Role of Endothelial Biomarkers in Patients With Coronary Artery Disease

Coronary artery disease is a contraction of the coronary arteries that prevent adequate blood supply to the heart muscle is called CAD. Usually caused by atherosclerosis, it may be advanced to the point where the heart muscle is injured due to lack of blood supply. Such damage may result in infarction, arrhythmias, and heart failure(1,2).

Telomeres are short in circulating leucocytes in patients with coronary artery disease but the precise mechanism is not well-known (3).

Telomere and telomerase are affected by cytomegalovirus (CMV) infection due to its effect on increasing the number of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA). Both genetic and environmental factors have been connected with individual distinction in TL.Cardiovascular risk factors such as smoking, diabetes mellitus, hypertension, obesity, and stress have been considered to upsurge inflammation, oxidative stress, therefore accelerating TL shortening (1,2)

It has also been observed that telomere loss in type 2 diabetic patients contributes to oxidative stress and endoplasmic reticulum stress while telomere shortening has also been proposed that it can serve as an independent risk factor of T2DM and it can measure disease progression(4).

Moreover, telomeric length in peripheral blood mononuclear cells (PBMCs) is associated with the duration of disease and good glycemic control seems to be protective for telomeric loss (5).

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor (TGF)-β superfamily. GDF-15, recently identified as one of the new cardioprotective cytokines. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk(6).

Dipeptidyl peptidase inhibitors (DPP4 -I) are called gliptins which increase the incretin levels and therefore prolong the post-prandial insulin action(7).

Diana et al reported that In type 2 diabetic patients, leukocyte telomere was significantly shorter than control groups and was significantly elongated after intervention by sitagliptin(8).

The common feature of all risk factors of CAD and T2DM imbalance between pro- and anti-oxidative factors in the organism with an increased production of reactive oxygen species (ROS).Nuclear factor erythroid-derived factor 2-related factor 2(Nrf2) is a family of transcription factors which plays an important role in protection against CVD and DM by regulating antioxidant enzymes in cells after ROS exposure (9).

In our study, we will propose a model, which would provide the basis to establish a marker for chronic reactivation of CMV and shed more light into the pathophysiology of CMV infection in patients with CAD in relation to GDF-15 and NrF2 and their implications on disease progression. Ultimately, this would then enable us to identify patients at risk and develop novel strategies for future treatment and prevention of heart diseases in our country. In light of our project research, the question arises whether telomere length could represent a marker of chronic CMV reactivation and uncertainty their length will be modified by the effect of DPP-4 or not?

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 with telomere length, GDF-15 \& NRF2.
4. We will detect the origin of our biomarkers by human umbilical vein endothelial cells(HUVECS).
5. We will measure the effect of DPP4-I (on TL \& GDF-15 on cardiac cell line).
6. We are looking to establish a new potential risk marker from our study, (GDF-15 \& NRF2) which could be tested in a larger cohort of patients. This would then enable us to identify CMV-seropositive patients at risk and develop novel strategies for future treatment and prevention.

Eligibility Criteria:
Inclusion Criteria:

1. According to American Heart Association, patients with a manifestation of myocardial ischemia and angina or angina equivalent (chest pain, abnormal stress testing) with or without T2DM.
2. All patients with risk factors such as hypertension, hyperlipidemia and smokers.

Exclusion Criteria:

1. Psycological disorders
2. Cancers.
3. Strock.
4. Acute and chronic inflammation and Autoimmune diseases were excluded from the study.