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Structural remodeling in hypertensive heart disease and the role of hormones
1Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212.
Insights
Hypertension and left ventricular hypertrophy increase cardiovascular risk due to myocardial fibrosis. The renin-angiotensin-aldosterone system and local angiotensin-converting enzyme activity drive this collagen accumulation, impacting heart structure and function.
Area of Science:
- Cardiovascular Medicine
- Pathology
- Molecular Biology
Background:
- Hypertension with left ventricular hypertrophy elevates cardiovascular event risk.
- Myocardial structural quality, not just mass, dictates cardiovascular risk.
- Fibrosis, including collagen accumulation and myocyte scarring, characterizes hypertensive heart disease.
Purpose of the Study:
- To investigate the structural basis of cardiovascular risk in hypertensive heart disease.
- To elucidate the role of the renin-angiotensin-aldosterone system in myocardial fibrosis.
- To identify local regulatory mechanisms of collagen turnover in the heart.
Main Methods:
- Morphological analysis of myocardial tissue.
- In vitro quantitative autoradiography to identify receptor binding.
- Investigation of renin-angiotensin-aldosterone system (RAAS) activation and its link to fibrosis.
Main Results:
- Hypertensive heart disease involves arteriolar remodeling and excessive adventitial collagen.
- Fibrosis is present in both hypertensive and normotensive ventricles, linked to RAAS.
- Receptors for angiotensin II, aldosterone, endothelin, and bradykinin are found in the myocardium.
- A nonendothelial angiotensin-converting enzyme (ACE) in fibrotic areas may regulate local angiotensin II and bradykinin.
Conclusions:
- Myocardial fibrosis, driven by RAAS and local ACE, contributes to cardiovascular risk in hypertension.
- A dysregulated balance favoring collagen synthesis over inhibition promotes fibrous tissue accumulation.
- Understanding these mechanisms is crucial for developing targeted therapies for hypertensive heart disease.
Abstract:
In hypertension, the risk of adverse cardiovascular events, including heart failure, is increased in the presence of left ventricular hypertrophy. Morphological studies suggest that it is not the quantity but rather the quality, or structure, of myocardium that confers such risk. Iterations in tissue structure that appear in hypertensive heart disease include a remodeling of intramyocardial coronary arterioles, similar to that found in systemic organs, and a disproportionate accumulation of fibrillar collagen within their adventitia and neighboring interstitial space. Microscopic scars replacing necrotic cardiac myocytes are also evident. These expressions of fibrosis appear in the normotensive, nonhypertrophied right and hypertensive, hypertrophied left ventricles and are linked to the renin-angiotensin-aldosterone system. Cardiac myocyte growth, the major determinant of myocardial mass, is related to ventricular loading. Mechanisms responsible for the reactive and reparative fibrosis with renin-angiotensin-aldosterone system activation are under investigation. In vitro quantitative autoradiography has identified angiotensin II, aldosterone, endothelin, and bradykinin receptors in the myocardium. A nonendothelial tissue angiotensin-converting enzyme, whose binding density is marked in the matrix of heart valves, adventitia, and sites of fibrosis, irrespective of its pathogenic basis, has also been found. This angiotensin-converting enzyme may be responsible for regulating local concentrations of angiotensin II and bradykinin that govern fibroblast collagen turnover. Based on a paradigm of discordant reciprocal regulation, in which a relative abundance of stimulators (eg, angiotensin II, aldosterone, and endothelins) of collagen synthesis exceeds inhibitors (eg, bradykinin, prostaglandins, and glucocorticoids), fibrous tissue appears.(ABSTRACT TRUNCATED AT 250 WORDS)