The Red Blood Cell as a Mediator and Therapeutic Target in Cardiovascular Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Red blood cell function defined as their ability to modulated post-ischemic recovery of left ventricular developed pressure, myocardial infarct size and endothelium-dependent relaxation.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 25 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Type 2 diabetes
排除标准
- 未提供
结局指标
主要结局
Red blood cell function defined as their ability to modulated post-ischemic recovery of left ventricular developed pressure, myocardial infarct size and endothelium-dependent relaxation.
时间窗: At 60 min of reperfusion
The function of red blood cells (RBCs) are investigated in isolated heart preparations and in isolated aorta. The heart preparations are subjected to ischemia followed by 60 min reperfusion and RBCs are administered into the coronary circulation at the onset of ischemia. Left ventricular developed pressure is recorded as readout of left ventricular function. Final infarct size is determined at the end of the reperfusion period. Isolated arteries are co-incubated with the RBCs for 18 h. Following the incubation, the arteries are mounted in myographs for the determination of endothelium-dependent and endothelium-independent relaxations.
次要结局
- Red blood cell production of reactive oxygen species(At baseline and following ex vivo inhibition of ROS formation.)
研究者
John Pernow
Professor
Karolinska Institutet