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LSU Health Shreveport Center for Cardiovascular Diseases and SciencesAnnual Report 2016

LSU Health Shreveport / Center for Cardiovascular Diseases and Sciences / Annual Report 2016

Director’s Letter

CCDS BOARD OF DIRECTORS

Monthly CCDS Activities

CCDS MEMBERS IN FOCUS GROUPS

GRANTS TO CCDS MEMBERS

TRAINEE HIGHLIGHTS

CCDS SPECIAL EVENTS

CCDS PUBLICATION HUGHLIGHTS

AWARDS

CCDS Member Technology DisclosureS

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Director’s LetterChris Kevil, PhD.

Dear Friends and Colleagues,

The Center for Cardiovascular Diseases and Sciences con-tinues to flourish and grow. While Louisiana still experiences disproportionately greater cardiovascular disease burden and mortality, our commitment to advance a greater understand-ing of cardiovascular disease and deliver life saving cardio-vascular care has never been greater.

In the subsequent pages, you will learn of the many accom-plishments of our CCDS faculty and students including, but not limited to: many new grant awards, new professional programs and networking events, participation and sponsor-ship of the International Society for Heart Research (ISHR), numerous publications of new discoveries, and advancement of new technologies and awarded patents. These achieve-ments are a testament to the passionate work and collegial and collaborative spirit among CCDS members.

Leadership within the CCDS continues to experience growth with the development of Assistant Director positions over-seeing Professional Development, Scientific Excellence, and Clinical and Translational Research. With our relentless pur-suit of research excellence, the Center is poised to enter an exciting new phase of growth and discovery leading the way here at LSU Health Shreveport and across the nation.

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Paari Dominic, Karen Stokes, Norma Phillips, Wayne Orr, Sara Krzywanski, Chris Kevil


CCDSBOARD OF DIRECTORS

D. Neil Granger, PhD, Chair (Physiology)

G E Ghali, DDS, MD, FACS, FRCS(Ed) (Chancellor and Dean)

Horacio D’Agostino, MD (Radiology)

Norman R. Harris, PhD (Physiology)

Sushil Jain, PhD (Pediatrics)

Christopher Kevil, PhD, Director (Pathology)

Alireza Minagar, MD (Neurology)

Glenn Mills, MD (Hematology/Oncology)

Anil Nanda, MD (Neurosurgery)

Dennis O’Callaghan, PhD (Microbiology)

Pratap Reddy, MD (Cardiology)

Sandra Roerig, PhD (Pharmacology)

Andrew Yurochko, PhD (Microbiology)

CCDS Leadership

Christopher Kevil, PhD, Director

A. Wayne Orr, PhD, Assistant Director for Professional Development

Karen Stokes, PhD, Assistant Director for Scientific Excellence

Paari Dominic, PhD, Assistant Director for Clinical and Translational Research

9/12/2016: Martha O’Donnell, PhD, University of California - Davis. “Exacerbated Brain Edema in Hyperglycemic Stroke: Cerebral Microvascular Na Transporters as Therapeutic Targets.”

10/03/2016: Kumuda Das, PhD, Texas Tech University Health Sciences Center. “Deglutathionylation of Coronary ENOS by Thioredoxin: Protective Role in Ischemia-reperfusion Injury of Heart.”

11/07/2016: William J. Pearce, PhD, Loma Linda University School of Medicine. “Fetal Programming in the Vasculature: Glucocorticoids, miRNA and Smooth Muscle Phenotype.”

12/052016: Ping He, MD, PhD, Penn State University - Hershey. “Circulating Microparticles and Diabetes-associated Microvascular Dysfunction.”

01/09/2017: Jeffrey Robbins, PhD, Cincinnati Children’s Hospital Medical Center. “Cardiac Disease: An Unfolding Story.”

02/06/2017: David G. Harrison, MD, Vanderbilt University School of Medicine. “Inflammation, Immunity and Hypertension.”

03/06/2017: Jun Chen, MD, University of Pittsburgh School of Medicine. “Microglial/Macrophage Responses After Cerebral Ischemia: A Double Edged Sword.”

04/03/2017: Hong Chen, PhD, Harvard Medical School. “The Role of Epsin In Vascular Biology.”

05/01/2017: David Y. Hui, PhD, University of Cincinnati College of Medicine. “Tissue-Specific Role of LRP1 in Cardiometabolic Disease Modulation.”

06/05/2017: Shayn Peirce-Cottler, PhD, University of Virginia. “Microvascular Network Remodeling: New Insights from In vivo Imaging and Computational Modeling.”

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Monthly CCDS ActivitiesCCDS Seminar Series


CCDS Clinical Conferences

01/11/2016: Department of Cardiology - Brijesh Patel, M.D. “Left Main Thrombosis and Coronary Perforation”

02/15/2016: Department of Interventional Radiology - Chaitanya Ahuja, M.D. “Catheter Directed Therapies in Acute Pulmonary Embolism”

03/15/2016: Department of Surgery - M. Andrew Sicard “Endovascular Repair of Mycotic Aneurysm” “Fenestrated Endovascular Aortic Arch Aneurysm Repair”

04/11/2016: Department of Nephrology - Mary Buffington, M.D. “Vascular Access Induced Hand Ischemia”

05/16/2016: Neurointerventional Radiology - Hai Sun, M.D. “Review of Treatments for Carotid Stenosis”

06/13/2016: Department of Surgery - Wayne Zhang, MD and Tze-Woei Tan, MD “LSUS CV Conference and International Vascular Symposium”

07/18/2016: Department of Radiology - Horacio D’Agostino, MD “Transarterial Embolization”

09/16/2016: Department of Nephrology - Sangeeta Pal, MD and Madeline Jimenez-Torres, MD “Case Conference Presentation”

10/17/2016: Department of Neurointerventional Radiology - Shymal Bir, MD, PhD FAHA “Is Concurrent Obstructive Sleep Apnea a Predictor of Poor Outcome for Intracranial Aneurysms?”

11/14/2016: Department of Surgery - Wayne Zhang, MD “LSA Fenestration During TEVAR” Chiranjiv Virk, MD “Celiac Artery Aneurysm Repair: Endovascular Approach”

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CCDS Clinical Conferences

01/23/2017: Department of Cardiology - Dr. Henock Zabher

02/13/2017: Department of Nephrology - Dr. Bakhtiar Mohamad Amin “Banding of AVF Fistula” Dr. Adrian Sequeira “Tunneled Dialysis Catheter Dysfunction”

03/13/2017: Department of Neurosurgery - Dr. Hai Sun “Moya Moya Disease”

04/10/2017: Department of Surgery - Dr. Chiranjiv Virk “Endovascular Intervention: Basic Concepts & Techniques”

05/08/2017: Department of Radiology - Dr. Chaitanya Ahuja

06/12/2017: Department of Cardiology - Dr. Henock Zabher

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CCDS Cardiovascular Trainee Group

09/12/2016: Role of sodium transporters in diabetic brain edema.

09/26/2016: eNOS modifications in ischemia reperfusion injury.

10/31/2016: miRNA regulation of smooth muscle cell phenotype.

11/28/2016: Microparticles in microvascular dysfunction.

01/03/2017: Dysregulated protein folding in cardiac disease.

01/30/2017: Role of circulating T cells in hypertension.

02/27/2017: Microglia in cerebral ischemia.

03/27/2017: Epsin in cardiovascular pathology.

04/24/2017: LRP1 in inflammation and atherosclerosis.

05/29/2017: Computational modeling of vascular networks.

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CCDS MEMBERS in Research Focus groupsVascular Biology

Basic ClinicalJonathan Steven Alexander, PhD (Physiology) Tak Yee Aw, PhD (Physiology) Felicity Gavins, PhD (Physiology) D. Neil Granger, PhD (Physiology) Norman R. Harris, PhD (Physiology) Lynn Harrison, PhD (Physiology) Sushil Jain, PhD (Pediatrics) Christopher Kevil, PhD (Pathology) David M. Krzywanski, PhD (Anatomy) Kevin McCarthy, PhD (Pathology) Sumitra Miriyala, PhD (Anatomy) Wayne Orr, PhD (Pathology) Manikandan Panchatcharam, PhD (Anatomy) Christopher Pattillo, PhD (Physiology)V. Hugh “Chip” Price Jr, DVM (Physiology) Karen Stokes, PhD (Physiology) Hong Sun, PhD (Anatomy) Matthew Woolard, PhD (Microbiology) Andrew Yurochko, PhD (Microbiology)

Paari Dominic, MD (Cardiology)Yufeng Dong, PhD (Orthopedics) Horacio D’Agostino, MD (Radiology) Sushil Jain, PhD (Pediatrics) Pavan Katikanini, MD (Cardiology) Christopher Kevil, PhD (Pathology)Marlyn Langford, PhD (Opthalmology)Massimo Morandi, MD (Orthopedics) Wayne Orr, PhD (Pathology)James Traylor, MD (Pathology)

Cardiac Biology Neurovascular Biology

Basic Basic

Clinical

Clinical

Shenu Bhuiyan, PhD (Pathology) Diana Cruz-Topete, PhD (Physiology)Paari Dominic, MD (Cardiology) Edward Glasscock, PhD (Anatomy) Sumitra Miriyala, PhD (Anatomy) Manikandan Panchatcharam, PhD (Anatomy)

Paari Dominic, MD (Cardiology) Horacio D’Agostino, MD (Radiology) Pavan Katikanini, MD (Cardiology) Kalgi Modi, MD (Cardiology) Pratap Reddy, MD (Cardiology)

Oleg Chernyshev, MD (Neurology)Horacio D’Agostino, MD (Radiology) Bharat Guthikonda, MD (Neurosurgery) Hung Wen Lin, PhD (Neurology)Alireza Minagar, MD (Neurology) Hyung Nam, PhD (Pharmacology) Anil Nanda, MD (Neurosurgery) Hugo Humberto Cuellar Saenz, MD (Neurosurgery)Hai Sun, MD (Neurosurgery)Yuping Wang, MD, PhD (OB-GYN)

J. Steven Alexander, PhD (Physiology)Felicity Gavins, PhD (Physiology) D. Neil Granger, PhD (Physiology) Kathryn Hamilton, PhD (Anatomy) Christopher Kevil, PhD (Pathology) David M. Krzywanski, PhD (Anatomy)Guohong Li, MD, PhD (Neurosurgery) Alireza Minagar, MD (Neurology) Hyung Nam, PhD (Pharmacology) Christopher Pattillo, PhD (Physiology)Xinggui Shen, PhD (Pathology) Karen Stokes, PhD (Physiology) Hong Sun, PhD (Anatomy)

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GRANTS TO CCDS MEMBERS

During the period of January 1, 2016 through June 30, 2017 the members of the CCDS received 17 research grant awards from the National Institutes of Health and other organizations such as the American Heart Association and the American Diabetes Association for a combined total of $5,458,623. Grant award information is listed below with respective CCDS members.

• Neurolymphatic Biomarkers in Neurodegeneration (Annette Funicello MS Research Foundation)

• 3D-Printing of Osteogenic Engineered Networks (OGEN) For Craniomaxillofacial Defects (Osteoscience Foundation)

• Sigma-1 Receptor and Cardioprotection (NIH)

• Investigating the dysfunction of the cerebral microvasculature in sickle cell disease (NIH)

• A novel role for neutrophils in sickle cell disease: new avenues to target cerebral microvascular dysfunction (AHA)

• Understanding cerebral microvasculature dysfunction in sickle cell disease (NIH)

• Complex genetic interactions in mouse model of sudden death in epilepsy (SUDEP) (NIH)

• Respiratory mechanisms of epilepsy with high risk of SUDEP (NIH)

• Neurocardiac mechanisms of epilepsy with high risk of SUDEP (NIH)

• Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) loss in diabetic retinopathy (AHA Predoctoral fellowship)

• Loss of the retinal glycocalyx in diabetes (NIH)

• R01 AT007442A (NIH)

• Hydrogen sulfide and vascular remodeling (NIH)

• Slit2/Robo1 regulation of diabetogenic T cell trafficking (ADA)

• Development of novel Anti-Cancer agents (NIH)

• Matrix specific signalling in endothelial cell dysfunction (NIH)

• Analytical lab on a chip device (Innolyzer)

• Clinical Impact of Ethnic Variation in Mitochondrial Function in Hypertension (LACaTS)

J. Steven Alexander

Md Shenuarin Bhuiyan

Felicity Gavins

Ed Glasscock

Norman Harris

Sushil Jain

Christopher Kevil

David Krzywanski

• Vascular Regulatory Mechanisms of Palmitic Acid Methyl Ester (NIH)

• Neuronal fatty acid methylation by protein arginine methyltransferase (AHA)

• Therapeutic potential of palmitic acid methyl ester against cerebral ischemia (AHA Postdoctoral Fellowship)

• Pharmacoproteomics of A2AR regulation in Alcoholism (BRF)

• Nck Adaptor Proteins in Atherogenic Endothelial Activation (NIH)

• Matrix-Specific Signaling in Endothelial Cell Dysfunction (NIH)

• Epha2 Mediates Vascular Smooth Muscle Fibroproliferative Response in Vascular Remodeling (AHA Predoctoral Fellowship)

• Influence of Glutathione on Ischemic Angiogenesis (AHA)

• Cytomegalovirus Exacerbates Microvascular Responses to Hypercholesterolemia Through the Activation of Neutrophils and Monocytes (AHA)

• Light Alcohol Consumption and Ischemic Stroke (NIH)

• Mechanism of chymase activation in endothelial cells (NIH)

• Macrophage-associated lipin-1 lipid synthesis regulates foam cell inflammatory responses (NIH)

• Contribution of myeloid-associated lipin-1 to macrophage pro-inflammatory responses (AHA Predoctoral Fellowship)

• Russian Tarragon inhibition of atherosclerosis (Pennington)

• Analysis of HCMV Infection of Monocytes and Macrophages (NIH)

Kevin Lin

Hugh Nam

Wayne Orr

Christopher Pattillo

Karen Stokes

Hong Sun

Yuping Wang

Matthew Woolard

Andrew Yurochko

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Trainee HighlightsChun (Mia) Li Malcolm Feist Postdoctoral Fellow, Graduate Research Day 2nd Place Poster Award Winner, Postdoctoral Division

Ischemic stroke continues to be one of the leading causes of death and permanent disability. Due to the advances in thrombolytic agents and intra-arterial therapy (IAP), transient focal cerebral ischemia has become one of the most common types of ischemic stroke. Although reperfusion is critical for restoring normal function, it paradoxically results in cerebral ischemia/reperfusion (I/R) injury. Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine leads to an increase in cerebral I/R injury by altering the balance between oxidant and antioxidant networks. Male Sprague-Dawley rats were divided into four groups: non-nicotine, nicotine (2 mg/kg/day for 4 weeks via an implanted subcutaneous osmotic minipump) group, Mito-Tempo treated non-nicotine and Mito-Tempo treated nicotine. Mito-Tempo (0.7mg/kg/day) was given intraperitoneally for 7 days prior to transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by intraluminal occlusion of the middle cerebral artery for 2 hours. Infarct size and neurological deficits were evaluated at 24 hours of reperfusion. Expression of adhesion molecules, tight junction (TJ) proteins, oxidants and antioxidants was measured using Western Blot analysis. Activity of matrix metalloproteinase (MMP)-9 and MMP-2 was determined by gelatin zymography. We found: First, four-week exposure of nicotine significantly downregulated basal expression of manganese superoxide dismutase (MnSOD), uncoupling protein-2 (UCP-2) and TJ proteins. Second, nicotine exposure significantly exacerbated infarct size and worsened neurological deficits following transient focal cerebral ischemia. Third, nicotine exposure significantly increased post-ischemic expression/activity of intercellular adhesion molecule-1 (ICAM-1) and MMP-2. Fourth, Mito-Tempo failed to attenuate the brain damage and improve neurological function in rats without nicotine exposure, but abolished nicotine exposure-induced elevation in cerebral I/R injury. Fifth, Mito-Tempo suppressed nicotine exposure-induced increase in post-ischemic expression of ICAM-1 and activity of MMP-2. Our findings suggest that nicotine may exacerbate cerebral I/R injury by increasing post-ischemic inflammation and blood-brain barrier (BBB) disruption via a mitochondrial oxidative stress.

Aimee Vozenelik Malcolm Feist Predoctoral Fellow, Graduate Research Day 1st Place Award Winner, Student Talks

Macrophage pro-inflammatory responses induced by oxidized low-density lipoproteins (oxLDL) mediate atherosclerosis progression. However, how oxLDL causes macrophages to become pro-inflammatory is still enigmatic. Macrophage foam cell formation induced by oxLDL requires glycerolipid synthesis. Lipin-1, a key enzyme in the glycerolipid synthesis pathway, contributes to oxLDL-elicited pro-inflammatory responses in a macrophage cell line. The objective of this study was to determine if myeloid-associated lipin-1 contributes to atherogenesis and asses its role in oxLDL-mediated signaling in macrophages. Our data demonstrate that myeloid-associated lipin-1 is atherogenic, likely through persistent activation of a PKCα/βII-ERK1/2-cJun signaling cascade that contributes to foam cell pro-inflammatory responses. Taken together these results suggest that oxLDL-induced foam cell formation and oxLDL-induced macrophage pro-inflammatory responses are not separate outcomes of oxLDL-stimulation of macrophages, but rather lipid synthesis that contributes to foam cell formation also influences macrophage inflammatory responses.

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Jungmi Winny Yun Malcolm Feist Predoctoral Fellow Jungmi Winny Yun, a fourth year student in Dr. Steve Alexander’s lab in the Department of Physiology, represented LSU Health Shreveport as an invited speaker at the 7th Annual International Society for Neurovascular Disease (ISNVD) meeting in Taormina, Italy.

Our objective is to explore the effects of pro-inflammatory cytokines (TNF-α and Interferon-γ) on the expression levels of neurolymphatic biomarkers in both brain endothelial cells as well as in microparticles shed from these cells. And to explore the functional effects of microparticles derived this way. We have also begun studying clinical samples (sera from healthy controls and MS patients) to investigate the expression levels and patterns of these markers in the sera and MPs isolated from them. Our in vitro experiments revealed that BECs release microparticles from both apical and basolateral domains. These MPs contained lymphatic markers, amyloid precursor protein (APP), as well as junctional markers, and interestingly caveolin-1, an important caveolar constituent. In our studies with clinical samples, we found that upon storage plasma microparticles appear to fission into smaller exosomes that liberate neurolymphatic biomarkers indicating that plasma is an unstable pool. Flow analysis of MPs for intracellular markers (e.g. actin) revealed that detergent permeabilization removes phosphatidylserine, the ligand for Annexin V used to detect MPs. Therefore we propose that the best approach is to analyze clinical samples is to use serum, instead of plasma; and perform immune analysis, instead of flow cytometric analysis, using immune blotting or protein binding ELISAs. We found that markers detected in plasma and sera are expressed by BECs, and that these markers change expression in response to inflammatory cytokines. This alteration corresponds with transfer of these markers into caveolae-rich microparticles, which therefore represent a circulating ‘snapshot’ of the vascular surface that can be analyzed by several immune approaches.

CCDS Special EventsMalcolm Feist Lecture

As part of the CV Seminar Series, one lecture a year in February is designated to be the Malcolm Feist Lecture on Translational Research in Cardiovascular Medicine. This special day honors the late Mr. Malcolm Feist and offers a venue to showcase the impact his gift has made to LSU Health Shreveport and cardiovascular research. A prominent translational cardiovascular researcher is invited to give the noon lecture, visit with the Malcolm Feist fellows, and attenda poster session highlighting the work of the CCDS trainees. This year’s speaker was David G. Harrison, MD, Vanderbilt University School of Medicine, whose lecture was titled, “Inflammation, Immunity and Hypertension.”

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Vikas Mishra and Dr. David Harrison, Malcolm Feist Guest Lecturer.

LSU Health Shreveport / Center for Cardiovascular Diseases and Sciences / Annual Report 2016 PAGE 13

Industry Day 2016

The CCDS serves as a resource for CV faculty to learn and promote com-mercialization of their discoveries, which may in turn lead to new approaches for treating CV disease. In addition to working with faculty in this area, the Center sponsors a yearly “Industry Day” for students, post-doctoral trainees, and faculty to learn about CV careers outside academia and the transition ofbiomedical research to industry. Speakers and topics for Industry Day 2016 were: Dr. Rona Scott, LSU Health Sciences Center Shreveport, “Epstein-Barr virus Induced Epithelial Reprogramming and Cancer”; Dr. Mehdi Keddache, Sequencing Specialist at Illumina, Inc., “Healthcare industry improvements made possible by unlocking the power of the genome”; Dr. Yuri Lvov, Louisiana Tech University, “Halloysite clay nanotubes in drug delivery”; and, Dr. Oswald Crasta, Genomic Breeding Lead and R&D Fellow, Dow AgroSciences, “Genomic Technologies for Pharmaceutical and Agricultural Applications.” The keynotes lectures were followed by an expert panel discussion focused on industry relationships and building startup compa-nies. The conference concluded with a poster session featuring the work of trainees and faculty from the participating institutions.

International Society for Heart Research (ISHR) 36th Annual Conference of the North American Section

The mission of the International Society for Heart Research is to promote the discovery and dissemination of knowledge in the cardiovascular sciences on a world-wide basis through publications, congresses and other media. Several CCDS faculty members actively participated in the 36th annual meet-ing of the North American Section of ISHR held in New Orleans, LA. The Cardiovascular Center was a platinum sponsor of this year’s event, whose donation supported the Young Investigator Travel Awards. The theme of the 2017 conference was “Translation of Cardiovascular Therapeutics to the Clinic.” There were approximately 300 attendees, mostly basic and transla-tional researchers in cardiovascular sciences.

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Gulf Coast Vascular Research Consortium Inaugural Meeting 2016

The Gulf Coast Vascular Research Consortium currently consists of 71 faculty members from 11 different institutions across Texas and Louisiana, including the LSU Health Sciences Center –Shreveport, Texas A&M, UT Health Sciences Center – San Antonio, Baylor College of Medicine, Houston Methodist Research Institute, MD Anderson, UT Health Sciences Center –Houston, UT Southwestern, Rice University, and NASA. The GVRC was established to leverage the existing strength of cardiovascular research in this region and the recent influx of several renowned leaders in the car-diovascular field to build collaborations between the various GVRC insti-tutions. The inaugural GVRC 2016 meeting was sponsored by the Center for Cardiovascular Diseases and Sciences at LSU Health Sciences Center Shreveport and held at the Shreveport Convention Center. 127 attendees (50 faculty and 77 trainees) from 13 institutions participated in the GVRC 2016 meeting.


CCDS Publication Highlights

Wu CYC, Lerner FM, Couto e Silva A, Neumann JT, Minagar A, Lin HW, Lee RHC. Utilizing the Modified T-Maze to Assess Functional Memory Outcomes after Cardiac Arrest. Journal of Visuailized Experiments. 2017. (In press)Lee RHC, Couto e Silva A, Lerner FM, Wilkins CS, Valido SE, Klein DD, Wu CY, Neumann JT, Della-Morte D, Koslow SH, Minagar A, Lin HW. Interruption of Perivascular Sympathetic Nerves of Cerebral Arteries Offers Neuroprotection Against Ischemia. Am J Physiol Heart Circ Physiol. 2017; 312(1): H182-H188.Becker F., Kurmaeva E., Gavins F., Stevenson E.V., Navratil A.R., Jin L., Tsunoda I., Orr A.W., Alexander J.S., and D. Ostanin. (2016) Ablation of CCR2 in acute and chronic colitis: two potentially independent roles for monocytes/macrophages in inflammation versus lymphangiogenesis. Inflamm. Bowel Dis., 22: 1326-1345.Yurdagul Jr. A. and A.W. Orr. (2016) Blood brothers: hemodynamics and cell-matrix interactions in endothelial function. Antioxid. Red. Sig., 25: 415-434.Yurdagul Jr. A., Finney A.C., Woolard M.D., and A.W. Orr. (2016) The Arterial Microenvironment: The Where and Why of Atherosclerosis. Biochem J., 473: 1281-1295.Yurdagul Jr. A., Sulzmaier F., Chen X.L., Pattillo C.B., Schlaepfer D.D., and A.W. Orr. (2016) Focal adhesion kinase activates RSK to drive NF-kB activation and endothelial proinflammatory gene expression by oxidized LDL. J. Cell Sci., 129: 1580-1591.Sugar T., Wassenhove-McCarthy D.J., Orr A.W., Green J., Esko J.D., van Kuppevelt T.H., and K.J. McCarthy. (2016) N-sulfation of heparan sulfate glycos-aminoglycans is a key, critical component of podocyte cell-matrix interactions. Am. J. Physiol. Renal Physiol., 310: F1123-F1135.Yuan S., Pardue S., Shen X., Alexander J.S., Orr A.W., and C.G. Kevil. (2016) Hydrogen sulfide metabolism regulates endothelial solute barrier functions. Redox Biol., 9: 157-166.Russel-Puleri S., Chattopadhyay M., Cancel L., Ebong E., Orr A.W., Frangos J.A., and J.M. Tarbell. (2017) Fluid shear stress induces upregulation of COX-2 and PGI2 release in endothelial cells via a pathway involving PECAM-1, PI3K, FAK, and p38. Am. J. Physiol. Heart Circ., 312: H485-H500.Finney A.C., Stokes K.Y, Pattillo C.P., and A.W. Orr. (2017) Integrin signaling in atherosclerosis. Cell. Mol. Life Sci., 74: 2263-2282.Finney A.C., Funk S.D., Green J.M., Yurdagul A. Jr., Rana M.A., Pistorius R., Henry M., Yurochko A.D., Pattillo C.B., Traylor J.G., Chen J., Woolard M.D., Kevil C.G., and A.W. Orr. (2017) EphA2 expression regulates inflammation and fibroproliferative remodeling in atherosclerosis. Circulation. 2017 Aug 8;136(6):566-582.

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Alam S., Abdullah C.S., Aishwarya R., Orr A.W., Traylor J.G., Miriyala S., Panchatcharam M., Pattillo C.B., and M.S. Bhuiyan. (2017) Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein (CHOP) expression in cardiomyocytes. Biosci Rep. 2017 Jul 16;37(4).Shinoda Y, Tagashira H, Bhuiyan MS, Hasegawa H, Kanai H, Zhang C, Han F, Fukunaga K. Corticosteroids Mediate Heart Failure-Induced Depression through Reduced σ1-Receptor Expression. PLoS One. 2016 Oct 14;11(10):e0163992. doi: 10.1371/journal.pone.0163992. eCollection 2016. PMID:27741227Bhuiyan MS, McLendon P, James J, Osinska H, Gulick J, Bhandary B, Lorenz JN, Robbins J. In vivo definition of cardiac myosin-binding protein C’s critical interactions with myosin. Pflugers Arch. 2016 Oct;468(10):1685-95. doi: 10.1007/s00424-016-1873-y. Epub 2016 Aug 27. PMID:27568194Shinoda Y, Tagashira H, Bhuiyan MS, Hasegawa H, Kanai H, Fukunaga K. Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction. J Pharmacol Sci. 2016 Jul;131(3):172-83. doi: 10.1016/j.jphs.2016.05.012. Epub 2016 Jun 4.Manna P, Achari AE, Jain SK. Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys. 2017 Feb 1;615:22-34.Achari AE, Jain SK. l-Cysteine supplementation increases insulin sensitivity mediated by upregulation of GSH and adiponectin in high glucose treated 3T3-L1 adipocytes. Arch Biochem Biophys. 2017 Sep 15;630:54-65. Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017;18. pii: E1321. Achari AE, Jain SK. L-Cysteine supplementation increases adiponectin synthe-sis and secretion, and GLUT4 and glucose utilization by upregulating disulfide bond A-like protein expression mediated by MCP-1 inhibition in 3T3-L1 adipo-cytes exposed to high glucose. Mol Cell Biochem 2016, 414: 105-13. Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling. Miriyala S, Thippakorn C, Chaiswing L, Xu Y, Noel T, Tovmasyan A, Batinic-Haberle I, Vander Kooi CW, Chi W, Latif AA, Panchatcharam M, Prachayasittikul V, Butterfield DA, Vore M, Moscow J, St Clair DK. Free Radic Biol Med. 2016 Feb;91:68-80.p62 Pathology Model in the Rat Substantia Nigra with Filamentous Inclusions and Progressive Neurodegeneration. Jackson KL, Lin WL, Miriyala S, Dayton RD, Panchatcharam M, McCarthy KJ, Castanedes-Casey M, Dickson DW, Klein RL. PLoS One. 2017 Jan 11;12(1):e0169291.

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PPARγ and Its Role in Cardiovascular Diseases. Chandra M, Miriyala S, Panchatcharam M. PAR Research, vol. 2017, Article ID 6404638, 10 pages, 2017.UCP2 upregulation promotes PLCγ-1 signaling during skin cell transformation. Sreedhar A, Lefort J, Petruska P, Gu X, Shi R, Miriyala S, Panchatcharam M, Zhao Y. Mol Carcinog. 2017 Oct;56(10):2290-2300.Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes. Alam S, Abdullah CS, Aishwarya R, Orr AW, Traylor J, Miriyala S, Panchatcharam M, Pattillo CB, Bhuiyan MS. Biosci Rep. 2017 Jul 16;37(4).Manganese superoxide dismutase deficiency triggers mitochondrial uncou-pling and the Warburg effect. Xu Y, Miriyala S, Fang F, Bakthavatchalu V, Noel T, Schnell DM, Wang C, St Clair WH, St Clair DK. Oncogene. 2017 Jul 13;36(28):4087.Ansari J, Yun JW, Kompelli AR, Moufarrej YE, Alexander JS, Herrera GA, Shackelford RE. The liquid biopsy in lung cancer. Genes Cancer. 2016 Nov;7(11-12):355-367. doi: 10.18632/genesandcancer.127. Review.White LA, Stevenson EV, Yun JW, Eshaq R, Harris NR, Mills DK, Minagar A, Couraud PO, Alexander JS. The Assembly and Application of ‘Shear Rings’: A Novel Endothelial Model for Orbital, Unidirectional and Periodic Fluid Flow and Shear Stress. J Vis Exp. 2016 Oct 31;(116). doi: 10.3791/54632.Yun JW, Xiao A, Tsunoda I, Minagar A, Alexander JS. From trash to trea-sure: The untapped potential of endothelial microparticles in neurovascular diseases. Pathophysiology. 2016 Dec;23(4):265-274. doi: 10.1016/j.patho-phys.2016.08.004. Epub 2016 Aug 12. ReviewYun, JW, Minagar, A, Alexander, JS. ‘Emerging Roles of Endothelial Cells in Multiple Sclerosis Pathophysiology and Therapy’ for ‘Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management, 2nd Ed., Springer press, 2017. Pgs 1-23.Mishra V, Karumuri BK, Gautier NM, Liu R, Hutson TN, Villalba SL, Vlachos I, Iasemidis L, Glasscock E. Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP). Human Molecular Genetics 2017, 26: 2091-2103. PMID: 28334922Jackson KL, Dhaibar HA, Dayton RD, Cananzi SG, Mayhan WG, Glasscock E, Klein RL. Severe respiratory changes at end stage in a FUS-induced disease state in adult rats. BMC Neuroscience 2016, 17: 69. PMID: 27793099

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Lee S, Holly K, Voziyanov V, Villalba S, Grigsby H, Glasscock E, Vlachos I, Murray T. Gradient index microlens implanted in prefrontal cortex of mouse does not affect behavioral test performance over time. PLoS ONE 2016, 11: e0146533. PMID: 26799938Hughes EL, Becker F, Flower RJ, Buckingham JC, Gavins FNE. Mast cells mediate early neutrophil recruitment and exhibit anti-inflammatory properties via the formyl peptide receptor 2/lipoxin A4 receptor. Br J Pharmacol. 2017 May 4.Becker F, Holthoff C, Anthoni C, Rijcken E, Alexander JS, Gavins FN, Spiegel HU, Senninger N, Vowinkel T. Downregulation of CX3CR1 ameliorates experi-mental colitis: evidence for CX3CL1-CX3CR1-mediated immune cell recruitment. Int J Colorectal Dis. 2016 Dec 10.Vital SA, Gavins FN. Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice. J Vis Exp. 2016 Oct 20.Holloway PM, Gillespie S, Becker F, Vital SA, Nguyen V, Alexander JS, Evans PC, Gavins FN. Sulforaphane Induces Neurovascular Protection Against a Systemic Inflammatory Challenge via Both Nrf2-Dependent and Independent Pathways. Vascul Pharmacol. 2016;85:29-38.Vital S, Becker F, Holloway PM, Perretti M, Granger DN, Gavins FNE. Fpr2/ALX Regulates Neutrophil-Platelet Aggregation and Attenuates Cerebral Inflammation. Impact For Therapy in Cardiovascular Disease. Circulation, 2016;133:2169-2179.Becker F, Kurmaeva E, Gavins FN, Stevenson EV, Navratil AR, Jin L, Tsunoda I, Orr AW, Alexander JS, Ostanin DV. A Critical Role for Monocytes/Macrophages During Intestinal Inflammation-associated Lymphangiogenesis. Inflamm Bowel Dis. 2016;22:1326-1345.Holloway PM, Gavins FNE. Modeling Ischemic Stroke in vitro: Status Quo and Future Perspectives. Stroke. 2016;47:561-569.Krzywanski, D.M., Westbrook, D.G., Moellering, D.R., Snary, K.D., Lipsey, C., Schurr, T.G., Vita, J., Dell’Italia, L., Ballinger, S.W. Endothelial Cell Bioenergetics and Mitochondrial DNA Damage Differ in Humans Having African or West Eurasian Maternal Ancestry. Circ Cardiovasc Genet. 2016 Feb;9(1):26-36.Leskov, I., Neville, A., Shen, X., Pardue, S., Kevil, C.G., Granger, D.N., Krzywanski, D.M. Nicotinamide nucleotide transhydrogenase activity impacts mitochondrial redox balance and the development of hypertension in mice. J Am Soc Hypertens. 2017 Feb;11(2):110-121.

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Wang B, Aw TY, Stokes KY. The protection conferred against ischemia-reper-fusion injury in the diabetic brain by N-acetylcysteine is associated with decreased dicarbonyl stress. Free Radic Biol Med. 2016;96:89-98. PMCID: PMC5079522.Finney AC, Stokes KY, Pattillo CB, Orr AW. Integrin Signaling in Atherosclerosis. Cell Mol Life Sci. 2017;74(12):2263-2282. PMCID: PMC5427000.Arif Yurdagul Jr, Alexandra C. Finney, Matthew D. Woolard, and A. Wayne Orr. (2016) The Arterial Microenvironment: The Where and Why of Atherosclerosis. Biochem J. 2016 May 15;473(10):1281-95. doi: 10.1042/BJ20150844.Jia X, Gu Y, Groome LJ, Al-kofahi M, Alexander JS, Li W, Wang Y. 1,25(OH)2D3 induces placental vascular smooth muscle cell relaxation by phosphorylation of myosin phosphatase target subunit 1Ser507: Potential beneficial effects of vitamin D on placental vasculature in humans. Biol Reprod 2016, 94(5): 116, 1-8. PMID: 27075619Wang Y, Dong Q, Gu Y, Groome LJ. Up-regulation of miR-203 expression induces endothelial inflammatory response: potential role in preeclampsia. Am J Reprod Immunol 2016, 76: 482-490. PMID: 27753461Jia X, Xu J, Gu Y, Gu X, Li W, Wang Y. Vitamin D suppresses oxidative stress-induced microparticle release by human umbilical vein endothelial cells. Biol Reprod 2017, 96(1): 199-210. PMID: 28395329Xu J, Jia X, Gu Y, Lewis DF, Gu X, Wang Y. 1,25(OH)2D3 reduces oxidative stress-induced procaspase-3/ROCK1 activation and MP release by placental trophoblasts. J Clin Endocrinol Metabolism 2017, 102(6): 2100-2110. PMID: 28368445Gu Y, Lewis DF, Alexander JS, Wang Y. Upregulation of cathepsin C expression contributes to endothelial chymase activation in preeclampsia. Hypertens Res. 2017 Sep 7. PMID28878298Xu J, Gu Y, Sun J, Lewis DF, Gu X, Wang Y. Reduced CD200 expression con-tributes to altered Th1/Th2 cytokine production in placental trophoblasts from preeclampsia. Am J Reprod Immunol. 2017 Sep 20. PMID28940677Wang Y: Vascular Biology of the Placenta. In Integrated Systems Physiology: Molecules to Function. 2nd Edition. Editors: Granger DN and Granger JP. Publisher: Morgan & Claypool Life Sciences, Princeton, USA, 2017. (doi: 10.4199/C00153ED1V01Y201704ISP075), San Rafael (CA): Morgan & Claypool Publishers; June 2017. ISBN-13: 978-1615047505Campadelli-Fiume, G, D. Collins-McMillen, T. Gianni, and A.D. Yurochko. 2016. Integrins as Herpesviruses’ Receptors and Mediators of the Host Signalosome. Annual Review of Virology. 3:215-236.

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Kim, J.H., D. Collins-McMillen, P. Caposio, and A.D. Yurochko. 2016. Viral binding induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes. Proc. Natl. Acad. Sci. U.S.A. 113:8819-8824.Kim*, J.H., D. Collins-McMillen*, F.D. Goodrum, and A.D. Yurochko. 2017. HCMV requires EGFR and PI(3)K signaling to enter and establish latency in CD34+ human progenitor cells. J Virol. 2017 Feb 14;91(5). *Denotes both authors contributed equally to the project.Yurochko, A.D. 2017. New mechanism by which human cytomegalovi-rus microRNAs negate the proinflammatory response to infection. mBio. 8:e00505-17.Collins-McMillen*, D.K, E.V. Stevenson*, G. Chan, M.T. Nogalski, and A.D. Yurochko. 2017. HCMV utilizes a non-traditional activation cascade of STAT1 via signaling through EGFR and integrins to promote survival and differentia-tion of HCMV-infected monocytes. J Virol. 2017 Oct 11. *Denotes both authors contributed equally to the project.Sreedhar A, Lefort J, Petruska P, Gu X, Shi R, Miriyala S, Panchatcharam M, Zhao Y. UCP2 Upregulation Promotes PLCγ-1 Signaling During Skin Cell Transformation. Mol Carcinog. 2017 Jun 2. doi: 10.1002/mc.22684.Sreedhar A, Zhao Y. Uncoupling protein 2 and metabolic diseases. Mitochondrion. 2017 Mar 25. pii: S1567-7249(17)30020-X. doi: 10.1016/j.mito.2017.03.005. [Epub ahead of print] ReviewShang X, Shu B, Wang Y, Luo Z, Wang G, Barton S, Morandi MM, Kevil CG, Dong Y. Human mesenchymal stromal cell sheet enhances allograft repair in a mouse model. Scientific Reports. 2017 7: 7982. DOI:10.1038/s41598-017-08804-2.Vora M, Kevil CG, Herrera GA. Contribution of human smooth muscle cells to amyloid angiopathy in AL (light-chain) amyloidosis. Ultrastruct Pathol. 2017 Aug 10:1-11. doi: 10.1080/01913123.2017.1349852. [Epub ahead of print] PubMed PMID: 28796568.Leskova A, Pardue S, Glawe JD, Kevil CG, Shen X. Role of thiosulfate in hydro-gen sulfide-dependent redox signaling in endothelial cells. Am J Physiol Heart Circ Physiol. 2017 Aug 1;313(2):H256-H264. doi: 10.1152/ajpheart.00723.2016. Epub 2017 May 26. PubMed PMID: 28550177.Yuan S, Shen X, Kevil CG. Beyond a gasotransmitter: hydrogen sulfide and polysulfide in cardiovascular health and immune response. Antioxid Redox Signal. 2017 Apr 11. doi: 10.1089/ars.2017.7096. [Epub ahead of print] PubMed PMID: 28398086.

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Kevil CG. Catalase as a regulator of reactive sulfur metabolism; a new inter-pretation beyond hydrogen peroxide. Redox Biol. 2017 Mar 24;12:528-529. doi: 10.1016/j.redox. 2017.03.018. [Epub ahead of print] PubMed PMID: 28363163; PubMed Central PMCID: PMC5374872.Kolluru G, Yuan S, Shen X, Kevil CG. Gasotransmitter Heterocellular Signaling. Antioxid Redox Signal. 2017 Jan 9. doi: 10.1089/ars.2016.6909. [Epub ahead of print] PubMed PMID: 28068782.D’Alessandro A, Nemkov T, Sun K, Liu H, Song A, Monte AA, Subudhi AW, Lovering AT, Dvorkin D, Julian CG, Kevil CG, Kolluru GK, Shiva S, Gladwin MT, Xia Y, Hansen KC, Roach RC. AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia. J Proteome Res. 2016 Oct 7;15(10):3883-3895. PubMed PMID: 27646145.Steiger AK, Pardue S, Kevil CG, Pluth MD. Self-Immolative Thiocarbamates Provide Access to Triggered H2S Donors and Analyte Replacement Fluorescent Probes. J Am Chem Soc. 2016 Jun 15;138(23):7256-9. doi: 10.1021/jacs.6b03780. Epub 2016 Jun 3. PubMed PMID: 27218691; PubMed Central PMCID: PMC4911618.Patel R, Yuan S, and Kevil CG. S-nitrosothiols and nitric oxide biology. In Nitric Oxide 3rd Edition. Edited by Bruce Freeman. Elseiver Press, 2017.Kevil CG, Cortese-Krott MM, Nagy P, Papapetroupulos A, Feelisch M, Szabo C. Cooperative interactions between NO and H2S: chemistry, biology, physiology, and pathophysiology. In Nitric Oxide 3rd Edition. Edited by Bruce Freeman. Elseiver Press, 2017.

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AWARDS• 2016, Outstanding Teacher Award, Department of Molecular and Cellular Physiology at LSU Health Shreveport

• Early Career Investigator (ECI) Travel Award. 36th Annual Meeting of the North American Section of International Society for Heart Research (ISHR), New Orleans LA

• Early Career Investigator (ECI) Travel awards. 36th Annual Meeting of the North American Section of International Society for Heart Research (ISHR), New Orleans LA

• BCVS Abstract Travel Award. American Heart Association’s Scientific Sessions 2016. New Orleans, LA

• 32nd Southern Biomedical Engineering Conference, 3rd place poster, 2016

• LSUHSC-S Neuroscience Research Day, Best student poster presentation, 2016

• Poster Award. 36th Annual Meeting of the North American Section of International Society for Heart Research (ISHR), New Orleans LA

• LSUHSC-S Neuroscience Research Day, Best postdoc poster presentation, 2016

• Poster Award. 36th Annual Meeting of the North American Section of International Society for Heart Research (ISHR), New Orleans LA

• PVD Travel Award for Young Investigators at the 2017 ATVB meeting

• American Association of Anatomists (AAA) Graduate Student Poster Award Finalist,2017

• AAA Annual Meeting at Experimental Biology, travel award, 2017

• LSUHSC-S Graduate Research Day, 2nd place oral presentation, 2017

• Partners Against Mortality in Epilepsy Conference, travel award, 2016

• American Heart AWRP 2017 Winter Predoctoral Fellowship.

• First place oral presentation at Graduate Research Day.

• 1st place - Graduate Research Day abstract book cover image contest.

• 2016 Society for Reproductive Investigation/Pfizer President’s Presenter Award Winner

• Zweifach Student Travel Award to the MCS Annual Meeting at Experimental Biology 2017

Junaid Ansari

Chowdhury Abdullah

Shafiul Alam

Hemangini Dhaibar

Vikas Mishra

Manikandan Panchatcharam

Bandana Shrestha

Krystle Trosclair

Stephanie Villalba

Aimee Vozenelik

Jie Xu

Winny Yun

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CCDS Member Technology Disclosures

Wayne Orr Targeting EphA2 for the treatment of fatty liver disease Targeting EphA2 for the treatment of fibroproliferative diseases

J. Winny Yun, J.S. Alexander and A. Minagar Use of Neurolymphatic Biomarkers of Endothelial Activation as a Diagnostic, Prognostic and Staging Approach in Neurodegenerative Disease

Yuping Wang Generation of nestin+/SOX2+/vimentin+mesenchymal stem cells/neural progenitor cells from the human placenta and treatment of neurodegenerative disorders Method for harvesting progenitor cells and method of treatment of kidney diseases, June 2016 (patent)

Chris Kevil - Issued Patents: Use of nitrite salts in chronic ischemia (Patent #9,649,334) Plasma H2S levels as biomarkers for vascular disease (Patent #9,599,602) Use of nitrite salts in treating tissue damage (Patent #9,579,344) Measurement of biologically labile hydrogen sulfide pools (Patent #9,465,024) CXCR4 and Robo1 expression as markers for autoimmune diabetes (Patent #9,234,886)

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March for Science in Shreveport,Saturday, April 22


Kimberly McCarter and Sergio Cananzi at the Malcolm Feist Poster Session.

Matthew Woolard, Alexandra Finney, Wayne Orr, Bandana Shrestha, Sumitra Miriyala, and Christopher Pattillo at ATVB 2017.

J. Winny Yun and Wayne Orr at the Malcolm Feist poster session.

Hugh Taylor, Jie Xu, Yuping Wang and Yoel Sadovsky at 2016 Society for Reproductive Investigation.

Shuai Yuan, Wayne Orr, Arif Yurdagul, and Zaki Al Yafeai at Gulf Coast Vascular Research Consortium.


Dr. Eung Soo Hwang, Andrew Yurochko and Jung Heon Kim at the International Meeting of the Federation of Korean Microbiological Societies.

Stephanie Villalba at the 2016 Partners Against Mortality in Epilepsy Conference.

Andrew Yurochko and Christopher Kevil at Red River Radio “Health Matters.”

Yuping Wang, J. Steven Alexander, Mahmoud Al-Kofahi and Norman Harris following Mahmoud’s successful dissertation defense.

D. Neil Granger, Randa Eshaq and Preeti Kanikarla at Graduate Research Day 2016.



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LSU Health Shreveport Center for Cardiovascular Diseases ... · LSU Health Shreveport Center for Cardiovascular Diseases and Sciences Annual Report 2016 CCDS Clinical Conferences