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Renin-angiotensin system: genes to bedside
F S Malik1, C J Lavie, M R Mehra
1Department of Internal Medicine, Ochsner Medical Institutions, New Orleans, LA 70121, USA.
Abstract:
Atherosclerosis and its vascular sequela are responsible for considerable morbidity and mortality rates. Several risk factors have been implicated in the pathogenesis of atherosclerosis, and the search for other risk factors continues on the medical horizon. Renin-angiotensin system (RAS), a multienzyme, multilocale axis, has been extensively studied as an important mediator of atherosclerosis. Recently, the tissue-based angiotensin system has been suggested as the most significant pathway of RAS. A genetic polymorphism in the human gene for the angiotensin-converting enzyme (ACE), one of the two enzymes of RAS, has been found to have a strong association with higher risk for acute coronary events, sudden cardiac death, vascular restenosis after angioplasty, and idiopathic and hypertrophic cardiomyopathy. Clinical and animal data support angiotensin II to be the final common pathway in the enzyme cascade of RAS and ACE as the key enzyme in the generation of Angiotensin II. ACE gene polymorphism appears to modify expression of cellular and free ACE levels and could represent a genetic marker for cardiovascular disease.
Insights
Genetic variations in the angiotensin-converting enzyme (ACE) gene are linked to increased cardiovascular disease risk. This ACE gene polymorphism may serve as a crucial genetic marker for conditions like atherosclerosis.
Area of Science:
- Cardiovascular Science
- Genetics
- Molecular Biology
Background:
- Atherosclerosis is a major cause of morbidity and mortality.
- The Renin-Angiotensin System (RAS) is implicated in atherosclerosis pathogenesis.
- Tissue-based RAS pathways are increasingly recognized as significant.
Purpose of the Study:
- To investigate the association between angiotensin-converting enzyme (ACE) gene polymorphism and cardiovascular disease risk.
- To explore the role of ACE gene variations in the pathogenesis of atherosclerosis and its sequelae.
Main Methods:
- Analysis of genetic polymorphism in the human ACE gene.
- Review of clinical and animal data on RAS and angiotensin II.
- Correlation of ACE gene variants with cardiovascular events and conditions.
Main Results:
- A strong association exists between ACE gene polymorphism and increased risk for acute coronary events, sudden cardiac death, and restenosis after angioplasty.
- ACE gene polymorphism is linked to idiopathic and hypertrophic cardiomyopathy.
- Angiotensin II is identified as a final common pathway in RAS, with ACE as the key enzyme.
Conclusions:
- ACE gene polymorphism may modify cellular and free ACE levels.
- ACE gene variations represent a potential genetic marker for cardiovascular disease.
- Understanding ACE gene's role is crucial for predicting and managing atherosclerosis and related conditions.