Role of Red Blood Cells in Cardiovascular Disease

Karolinska Institute

Status: Enrolling

Conditions: Diabetes Mellitus

Study type: Observational

Funder types: Other

Identifiers

NCT07151222

2024-02534

Details and patient eligibility

About

The risk of myocardial infarction is dependent on cardiovascular risk factors including type 2 diabetes (T2D) but underlying mechanisms are poorly understood. We identified that red blood cells (RBCs) mediate beneficial cardiovascular regulatory effects under hypoxic/ischemic conditions via signaling by nitric oxide (NO) and soluble guanylate cyclase (sGC) in the RBCs. The RBCs become dysregulated in T2D which induces endothelial and cardiac injury. This project investigates the signaling of RBCs in cardiovascular disease and explores novel therapeutic strategies that target RBC function in myocardial infarction and T2D.

Aims To determine the

• mechanisms behind cardioprotective effect of RBCs in myocardial infarction
• signaling behind cardiovascular injury induced by RBCs in T2D

Work plan RBCs collected from patients with myocardial infarction, patients with T2D and healthy controls are investigated in bioassays including isolated hearts of ischemia/reperfusion, endothelial function and cell cultures. Molecular mechanisms behind the effects of RBCs are identified with focus on the NO-sGC pathway in the RBCs.

This project unravels the RBC as a mediator of cardiovascular disease and has the potential to identify novel therapeutic strategies by targeting RBC signaling.

Full description

The function of RBCs are investigated in functional bioassays and cell culture systems. The bioassays include isolated hearts subjected to ischemia-reperfusion and isolated arteries. the readouts are left ventricular function, infarct size and endothelial function . Comparisons are made between RBCs collected from patients with cardiovascular disease, type 2 diabetes and healthy controls. Pharmacological interventions are performed by ex vivo incubations with focus on the NO-sGC pathway.

Enrollment: 500 estimated patients

Sex: All

Ages: 25 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Type 2 diabetes

Exclusion criteria

-

Trial design

500 participants in 4 patient groups

Type 2 diabetes

Description:

Patients with type 2 diabetes

Type 1 diabetes

Description:

Patients with type 1 diabetes

Coronary artery disease/Myocardial infarction

Description:

Patients with acute coronary syndromes

Healthy controls

Description:

Age- and gender-matched healthy subjects