The Role of a Dysfunctional Renin-Angiotensin System in the Development of Vascular Disease
Shohaib Virani
Introduction. Vascular disease is a broad array of disorders, including atherosclerosis, peripheral artery disease, aneurysms and blood clotting disorders, which can ultimately be tied to a damaged endothelium2. Vascular disease is associated with currently associated with old age, diabetes, smoking, and uncontrolled hypertension4. However, there have been recent hypotheses that indicate that the dysregulation of the renin-angiotensin-aldosterone system (RAAS) can cause damage to the endothelial lining of blood vessels, predisposing an individual to developing vascular disease1,3-6. Therefore, overexpression of RAAS can lead to early aging and diminish cardio-protective molecules of the body1,2. Due to these findings, the underlying mechanism of developing vascular disease can be identified and treated preventing the development of vascular complications, such as, stroke, occlusion, and peripheral ischemia. Methods. Mice were separated into groups based on the amount of angiotensin receptor type 2 (ATR2) transgene that was expressed. Three groups were made: mice with 1 copy, mice with 4 copies and mice with 9 copies. These mice were then monitored for 12 weeks before an artificial myocardial infarction was induced. The mice were then monitored again for 4 weeks. Results. Prior to the artificial MI, the number of ATR2 receptor transgenes did not correlate with the abnormalities in heart rate, blood pressure, or cardiac function. In the week following MI, 36% of the wild type mice, 11% of mice with 1 ATR2 transgene, 23% of mice with 4 ATR2 transgenes, and 31% of mice with 9 ATR2 transgenes died1. Studies also show that increases in angiotensin converting enzyme and angiotensin II as one ages contribute to the pro-inflammatory increase in size of the aorta3. Conclusions. Studies have indicated that RAAS can have a protective effect on vasculature if expressed in appropriate amounts, but the overexpression of RAAS can have detrimental pro-inflammatory affects that can contribute to the development of vascular disease.
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