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

February 15, 2021 updated by: Klinik für Kardiologie, Pneumologie und Angiologie, Heinrich-Heine University, Duesseldorf

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

Study Type

Observational

Enrollment (Actual)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Germany
- - Duesseldorf, Germany, 40225
    - University Hospital Duesseldorf

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

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 Time Frame: baseline, 3 hours and 3 month	baseline, 3 hours and 3 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deformability and stability of red blood cell membrane Time Frame: baseline, 3 hours and 3 month	by Laser assisted Optical Rotational Cell Analyzer (LORCA)	baseline, 3 hours and 3 month
Microvascular function Time Frame: baseline, 3 hours and 3 month	Determination of microvascular function with Laser-Doppler Perfusion Imaging	baseline, 3 hours and 3 month
Peripheral and central hemodynamic measurement Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Determination of arterial stiffness Time Frame: baseline, 3 hours and 3 month	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 Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Determination of nitrate and nitrite in blood plasma and red blood cells (RBC) Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Determination of nitric oxide and cyclic guanosine monophosphate (cGMP) in blood plasma and in red blood cells Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Determination of endothelial microparticles Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Electrocardiogram Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Aging and turnover of red blood cells Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Redox status of red blood cells Time Frame: baseline, 3 hours and 3 month	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 Time Frame: baseline, 3 hours and 3 month	Determination of aggregation of red blood cells with LORCA	baseline, 3 hours and 3 month
Platelet aggregometry Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month
Expression and function of soluble guanylyl cyclase (sGC) in red blood cells Time Frame: baseline, 3 hours and 3 month	measurement of enzyme expression and activity	baseline, 3 hours and 3 month
Expression and activity of Protein Kinase G (PKG) Time Frame: baseline, 3 hours and 3 month	measurement of enzyme expression and activity	baseline, 3 hours and 3 month
Determination of leucocyte populations and leucocyte function Time Frame: baseline, 3 hours and 3 month	flow-cytometry	baseline, 3 hours and 3 month
Changes of tetrahydrobiopterin-metabolism Time Frame: baseline, 3 hours and 3 month		baseline, 3 hours and 3 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heinrich-Heine University, Duesseldorf

Investigators

Principal Investigator: Malte Kelm, Prof. MD, Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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