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Effect of the renin-angiotensin-aldosterone system on the cardiac interstitium in heart failure
1Zentrum für Innere Medizin, Abteilung Kardiologie, Klinikum der Philipps-Universität, Marburg.
Insights
The renin-angiotensin-aldosterone system (RAAS) hormones, angiotensin II and aldosterone, drive cardiac fibroblast growth and collagen deposition in heart failure. Targeting the RAAS may offer therapeutic benefits for myocardial remodeling and dysfunction.
Area of Science:
- Cardiology
- Biochemistry
- Physiology
Background:
- Chronic heart failure involves complex interactions between the renin-angiotensin-aldosterone system (RAAS) and cardiac remodeling.
- Hemodynamic overload leads to myocardial hypertrophy and fibroblast activation, contributing to pathological cardiac changes.
Purpose of the Study:
- To investigate the role of RAAS effector hormones, angiotensin II and aldosterone, in regulating cardiac fibroblast activity and myocardial collagen matrix remodeling.
- To explore the potential therapeutic implications of targeting the RAAS in heart failure management.
Main Methods:
- In vivo and in vitro studies were conducted to examine the effects of angiotensin II and aldosterone on cardiac fibroblasts.
- Assays were performed to measure collagen synthesis and matrix metalloproteinase I activity in cultured cardiac fibroblasts.
Main Results:
- Angiotensin II and aldosterone were found to stimulate collagen synthesis in cultured adult cardiac fibroblasts.
- Angiotensin II was also shown to inhibit matrix metalloproteinase I activity, reducing collagen degradation.
- These hormonal actions contribute to the accumulation of interstitial collagen and myocardial stiffness.
Conclusions:
- The RAAS plays a critical role in the structural remodeling of the myocardial collagen matrix, independent of direct hemodynamic load.
- Findings support the rationale for therapeutic strategies involving angiotensin converting enzyme inhibition or RAAS blockade in managing heart failure.
- Targeting the RAAS may help mitigate pathological cardiac hypertrophy and improve cardiac function in patients with various forms of heart disease.
Abstract:
The interaction of the renin-angiotensin-aldosterone system (RAAS) and cardiac growth is of great interest in chronic heart failure. The pressure or volume overloaded heart shows a hypertrophic growth of the myocardium, i.e., an enlargement of cardiac myocytes. In addition, cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intramyocardial coronary arteries. This remodeling of the cardiac interstitium represents a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness, leading to ventricular diastolic and systolic dysfunction and ultimately the appearance of symptomatic heart failure. The growth of cardiac fibroblasts is not primarily regulated by the hemodynamic load. In vivo and in vitro studies suggest that the effector hormones, angiotensin II and aldosterone, of the RAAS are primarily involved in regulating the structural remodeling of the myocardial collagen matrix. In cultured adult cardiac fibroblasts, angiotensin II and aldosterone has been shown to stimulate collagen synthesis while angiotensin II additionally inhibits matrix metalloproteinase I activity, which is the key enzyme for interstitial collagen degradation in the myocardium. These findings may serve as rationale for a remedial therapy with angiotensin converting enzyme inhibition or blockage of the RAAS in congestive heart failure in patients with hypertensive heart disease, post myocardial infarction or with dilated cardiomyopathy.