Regulation and Signaling of Red Blood Cell (RBC) Endothelial Nitric Oxide Synthase (eNOS) in Patients With Stable and Unstable Coronary Artery Disease

Study Overview
=================
Brief Summary
-----------------
The aim of this study is measurement of expression and activity of RBC eNOS in different clinical cohorts of patients with coronary artery disease and acute coronary syndrome and to investigate the importance of the NO-stimulated reaction cascade in terms of sGC and PKG.

Official Title
-----------------
Regulation and Signaling of RBC-eNOS in Patients With Stable and Unstable Coronary Artery Disease

Conditions
-----------------
Coronary Artery Disease, Endothelial NO-synthase

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: informed consent for ACS(acute coronary syndrome)-Group: angiographic coronary artery disease; acute coronary syndrome, defined by EITHER unstable angina pectoris with significant coronary stenosis (troponin negative, without significant ST-elevation) OR low-risk NSTEMI (Troponin positive, without significant ST-elevation) for stable CAD-Group: angiographic coronary artery disease; no acute coronary syndrome within the last 3 months healthy control group: No clinical or angiographical signs of apparent atherosclerosis Exclusion Criteria: acute inflammation (CRP > 1 mg/dl, leukocyte > 11.000/µl) malignant diseases pregnancy medication with NO-donors ( e.g.isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate, Molsidomin, Ranexa) patients with STEMI or high-risk NSTEMI

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with CAD<br>Patients with stable coronary artery disease | |
| Patients with ACS<br>Patients with acute coronar syndrome, instable Angina pectoris and low-risk NSTEMI | |
| healthy control group<br>healthy control group without clinical apparent arteriosclerosis | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of red cell endothelial nitric oxide-synthase (eNOS)-expression and - activity |  | baseline, 3 hours and 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deformability and stability of red blood cell membrane | by Laser assisted Optical Rotational Cell Analyzer (LORCA) | baseline, 3 hours and 3 month | 
| Microvascular function | Determination of microvascular function with Laser-Doppler Perfusion Imaging | baseline, 3 hours and 3 month | 
| Peripheral and central hemodynamic measurement |  | baseline, 3 hours and 3 month | 
| Determination of arterial stiffness | Determination of arterial stiffness with pulse wave analysis during blood pressure measurement or echocardiography. | baseline, 3 hours and 3 month | 
| determination of flow-mediated dilation |  | baseline, 3 hours and 3 month | 
| Determination of nitrate and nitrite in blood plasma and red blood cells (RBC) |  | baseline, 3 hours and 3 month | 
| Determination of nitric oxide and cyclic guanosine monophosphate (cGMP) in blood plasma and in red blood cells |  | baseline, 3 hours and 3 month | 
| Determination of endothelial microparticles |  | baseline, 3 hours and 3 month | 
| Electrocardiogram |  | baseline, 3 hours and 3 month | 
| Aging and turnover of red blood cells |  | baseline, 3 hours and 3 month | 
| Redox status of red blood cells | Determination of redox status of red blood cells will be measured on free thiole with thioltracker and reactive oxygen species( ROS) by dihydrodichlorofluorescein | baseline, 3 hours and 3 month | 
| Aggregation of red blood cells | Determination of aggregation of red blood cells with LORCA | baseline, 3 hours and 3 month | 
| Platelet aggregometry |  | baseline, 3 hours and 3 month | 
| Expression and function of soluble guanylyl cyclase (sGC) in red blood cells | measurement of enzyme expression and activity | baseline, 3 hours and 3 month | 
| Expression and activity of Protein Kinase G (PKG) | measurement of enzyme expression and activity | baseline, 3 hours and 3 month | 
| Determination of leucocyte populations and leucocyte function | flow-cytometry | baseline, 3 hours and 3 month | 
| Changes of tetrahydrobiopterin-metabolism |  | baseline, 3 hours and 3 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coronary artery disease, acute coronary syndrome, angina pectoris, non-ST-segment elevation myocardial infarction, red blood cells, erythrocytes