Role of endothelial Biomarkers in Patients with Conroy artery

diseases

Coronary artery disease

.

CAD, is a narrowing of the coronary

arteries that prevent adequate blood

supply to the heart muscle is called CAD.

Usually caused by atherosclerosis , it

may progress to the point where the

heart muscle is damaged due to lack of

blood supply. Such damage may result in

infarction, arrhythmias and HF.

.

Recent studies in diverse populations

have reported an association of shorter

telomeres in circulating leukocytes with

CAD (Haoran et al.,2017) . The exact

mechanisms connecting short telomeres

and CAD are yet to be established.

.

Coronary artery disease and telomere length

.

In clinical practice, shorter TL reflects

the burden of oxidative stress and

inflammation, and might be an effective

biomarker for risk stratification for

atherosclerosis and CVDs.

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Cytomegalovirus and telomere

Cytomegalovirus (CMV) infection may be

particularly important for telomere and

telomerase dynamics due to its dramatic

impact on peripheral blood lymphocyte

composition by increasing the number and

proportions of highly differentiated T cells

that are characterized by shorter telomere

length (TL) and lowered telomerase activity

(TA)

Type 2 diabetes mellitus and telomere length

The β cell apoptosis is an indispensiblecondition for the pathogenesis ofT2DM.

Telomere shortening considered to bethe main cause of apoptosis of betacells and other organs such as kidneys,eyes and peripheral nerves.

1. Growth differentiation factor-

15 (GDF-15)

Is a target biomarker in CAD and T2DM.

It is highly expressed in cardiomyocytes in

normal and pathological condition.

2. Nuclear factor-E2 related factor(NRF2)

The common feature of all risk factors ofCAD and T2DM imbalance between pro-and anti-oxidative factors in the organismwith an increased production of reactiveoxygen species (ROS).(Nrf2) is a family of transcription factors which plays an important role in protection against CVD and DM.

AIMS OF THE STUDY

1) We are aiming to establish a marker for

chronic reactivation and pathophysiology

of CMV infection in patients with coronary

artery disease.

2) We will be able to answer whether there

is a link between the seropositive CMV ,

telomere length and CAD.

3)We will correlate the seropositive CMV withTL , GDF-15 & NRF2.

Study Design

1. We will recurit 45 CAD patients (20-55 years)

[±T2DM] attending to Cardiology Department,

Assuit University Hosiptal,

2. Fourty Five (age-matched patients ) healthy

volunteers with normal angiogram, will recruit in

the present study after obtaining an informed

consent with lack any history of cancer,

inflammatory disease and immune disorders

3-CMV serostatus: CMV serostatus will be

determined by using the Anti CMV/IgG and IgM

by (Rapid Test Cassette /Spectrum ).

1-Patients with CAD have been shown to

have shorter telomeres reflect the burden of

oxidative stress and inflammation. So-called

telomere theory that shorter telomeres will

contribute in part to the pathogenesis of

CAD.

1. CMV immediate early genes may inhibit the function of p53, contributing to smooth muscle proliferation and accumulation by blocking p53's inhibition of cell-cycle progression.

2. We speculate that the ability of human CMV to prevent apoptosis plays a role in postangioplasty restenosis, transplantation arterio-obliteration, and atherosclerosis.

2-Our study is the first to test the association of the highly

common constant CMV infection with CAD .

constant with our theory, we will expect that CMV

seropositive patients will be associated with short TL, high

plasma level of GDF15 and NRF2.

This would then enable us to identify CMV seropositive

patients to develop novel strategies for future treatment and

prevention of CAD.

Results•Telomere length of the type 2 diabetic patients

(1.58±0.57) was significantly shorter than those of

control subjects (3.98±0.90)

•and was significantly

•Elongated after intervention by sitagliptin. There was

no significant difference between the T2D and control

group in telomerase activity, and the treatment of

sitagliptin inT2D group showed no significant effect on

the telomerase activity.

• In type 2 diabetes patients, leukocyte telomere length is significantly reduced, whereas the telomerase activity seems less influenced. Sitagliptin might protect β-cells in the pancreas by elongating the telomere length.

Percentage of GDF-15 Concentration and TL in cardiac patients with or without DM versus

controls

• Compared with controls. The distribution of GDF-15 in the CAD group was significantly higher than HC group (P<0.01). After linear correlation analysis, the expression level of GDF-15 was found to be positively related to the degree of CAD prognosis .

Thus :• GDF-15 might involve in the

development and maintenance of CAD rheumatic heart disease, and GDF-15 could be used as a novel biomarker to evaluate atherosclerosis and fibrosis as well in the future.

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Conclusions • We confirmed that Telomere shortening in patients with CAD could

potentially be recognized to either inherited TL shortening or acquired

accelerated telomere shortening

• In addition,cytomegalovirus-seropositive patients but not healthy

control subjects demonstrated further shortening of their cytotoxic T

lymphocytes. Surprisingly, TL shortening in CAD patients demonstrated

a very strong correlation with cardiac dysfunction, which suggests a

automatic link between CAD and immunity system .

• Anti-inflammatory and antioxidant effects of gliptin.

Thank You