Ignite Creation Date:
2024-05-06 @ 10:02 AM
Last Modification Date:
2024-10-26 @ 12:23 PM
Study NCT ID:
NCT03146208
Status:
UNKNOWN
Last Update Posted:
2017-05-09
First Post:
2017-05-06
Brief Title:
Role of Endothelial Biomarkers in Patients With Coronary Artery Disease
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Biomarkers of Coronary Artery Diseases
Status:
UNKNOWN
Status Verified Date:
2017-05
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 failure12
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 TLCardiovascular risk factors such as smoking diabetes mellitus hypertension obesity and stress have been considered to upsurge inflammation oxidative stress therefore accelerating TL shortening 12
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 progression4
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 risk6
Dipeptidyl peptidase inhibitors DPP4 -I are called gliptins which increase the incretin levels and therefore prolong the post-prandial insulin action7
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 sitagliptin8
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 ROSNuclear factor erythroid-derived factor 2-related factor 2Nrf2 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
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 TLCardiovascular risk factors such as smoking diabetes mellitus hypertension obesity and stress have been considered to upsurge inflammation oxidative stress therefore accelerating TL shortening 12
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 progression4
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 risk6
Dipeptidyl peptidase inhibitors DPP4 -I are called gliptins which increase the incretin levels and therefore prolong the post-prandial insulin action7
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 sitagliptin8
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 ROSNuclear factor erythroid-derived factor 2-related factor 2Nrf2 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
Detailed Description:
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 cellsHUVECS
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
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 cellsHUVECS
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None