The clinical investigator

, Volume 71, Issue 5, pp S35–S41

Renin-angiotensin system and myocardial collagen matrix remodeling in hypertensive heart disease: in vivo and in vitro studies on collagen matrix regulation

  • C. G. Brilla
  • B. Maisch
  • K. T. Weber
Original Articles RAS and Collagen Metabolism


The interstitial space of the myocardium is composed of nonmyocyte cells and a highly organized collagen network which serves to maintain the architecture and mechanical behavior of the myocardial walls. It is the myocardial collagen matrix that determines myocardial stiffness in the normal and structurally remodeled myocardium. In hypertensive heart disease, the heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for collagen synthesis and degradation, explains the appearance of diastolic and/or systolic dysfunction of the left ventricle that leads to symptomatic heart failure. Several lines of evidence suggest that circulating and myocardial renin-angiotensin systems (RAS) are involved in the regulation of the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition that was found to prevent myocardial fibrosis in the rat with renovascular hypertension. In cultured adult rat cardiac fibroblasts angiotensin II was shown to directly stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation, that would lead to collagen accumulation. In the spontaneously hypertensive rat, an appropriate experimental model for primary hypertension in man, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness due to interstitial fibrosis could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease.

Key words

Myocardial fibrosis Arterial hypertension Cardiac renin-angiotensin system ACE inhibition 


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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • C. G. Brilla
    • 1
  • B. Maisch
    • 1
  • K. T. Weber
    • 2
  1. 1.Innere Medizin, SP KardiologieKlinikum der Philipps-Universität MarburgGermany
  2. 2.Department of MedicineUniversity of Missouri-ColumbiaColumbia
  3. 3.Innere Medizin SP KardiologieKlinikum der Philipps-Universität MarburgMarburgGermany

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