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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Endothelial NO-synthase

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Germany
  • Duesseldorf, Germany, 40225
    • University Hospital Duesseldorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

3 groups:

• ACS group (100 Patients)
• stable CAD group (100 Patients)
• healthy control group (100 Healthy Volunteers)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patients with CAD; Patients with stable coronary artery disease
Patients with ACS; Patients with acute coronar syndrome, instable Angina pectoris and low-risk NSTEMI
healthy control group; healthy control group without clinical apparent arteriosclerosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Principal Investigator: Malte Kelm, Prof. MD, Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 9, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: coronary artery disease; angina pectoris; acute coronary syndrome; red blood cells; erythrocytes; non-ST-segment elevation myocardial infarction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: RBC in CAD; 13-037 (Other Identifier: CTSU)