Pathologic hypertrophy with fibrosis

The structural basis for myocardial failure

Karl Weber, Christian G. Brilla, Scott E. Campbell, Guoping Zhou, Luiz Matsubara, Eduardo Guarda

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The major risk factor associated with the appearance of adverse cardiovascular events and outcome attributable to cardiovascular disease is left ventricular hypertrophy (LVH). Why this should be so resides not in the increase in myocardial mass per se, but in the disruption of myocardial structure. An abnormal accumulation of fibrillar collagen within the adventitia of intramyocardial coronary arteries and neighboring interstitial spaces represents such a distortion in structure. Furthermore, this fibrosis disrupts the electrical and mechanical behavior of the hypertrophied myocardium. Mechanisms responsible for fibrillar collagen accumulation have been examined in intact animals and cultured cardiac fibroblasts. In vivo studies indicate that myocardial fibrosis is associated with the presence of chronic mineralocorticoid excess, relative to sodium intake and excretion, not hemodynamic workload. Accordingly, fibrosis can appear in both the hypertensive, hypertrophied and nonhypertensive, nonhypertrophied ventricles. In both primary and secondary hyperaldosteronism it was possible to prevent myocardial fibrosis with an aldosterone receptor antagonist, while in unilateral renal ischemia angiotensin converting enzyme (ACE) inhibition was similarly cardioprotective. A regression in fibrous tissue and normalization of diastolic stiffness has also been possible using ACE inhibition, bringing forward the concept of cardioreparation and the notion that heart failure due to fibrosis may be reversible. In vitro studies indicate that effector hormones of the renin-angiotensin-aldosterone system stimulate fibroblast collagen synthesis. Aldosterone, in pathophysiologic concentrations, and angiotensin II, in much larger concentrations, each enhance collagen synthesis without altering the mitogenic potential of these cells. Thus, elevations in circulating aldosterone and angiotensin II, relative to sodium intake, have the potential to not only alter sodium homeostasis and vascular tonicity, but also the structure of cardiovascular tissue. Thus, myocardial fibrosis represents a structural basis for pathologic hypertrophy and ultimately accounts for the appearance of adverse cardiovascular events and outcomes.

Original languageEnglish (US)
Pages (from-to)75-85
Number of pages11
JournalBlood Pressure
Volume1
Issue number2
DOIs
StatePublished - Jan 1 1992

Fingerprint

Hypertrophy
Fibrosis
Heart Failure
Fibrillar Collagens
Sodium
Peptidyl-Dipeptidase A
Aldosterone
Angiotensin II
Collagen
Fibroblasts
Mineralocorticoid Receptor Antagonists
Adventitia
Mineralocorticoids
Hyperaldosteronism
Left Ventricular Hypertrophy
Renin-Angiotensin System
Workload
Blood Vessels
Coronary Vessels
Myocardium

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Weber, K., Brilla, C. G., Campbell, S. E., Zhou, G., Matsubara, L., & Guarda, E. (1992). Pathologic hypertrophy with fibrosis: The structural basis for myocardial failure. Blood Pressure, 1(2), 75-85. https://doi.org/10.3109/08037059209077497

Pathologic hypertrophy with fibrosis : The structural basis for myocardial failure. / Weber, Karl; Brilla, Christian G.; Campbell, Scott E.; Zhou, Guoping; Matsubara, Luiz; Guarda, Eduardo.

In: Blood Pressure, Vol. 1, No. 2, 01.01.1992, p. 75-85.

Research output: Contribution to journalArticle

Weber, K, Brilla, CG, Campbell, SE, Zhou, G, Matsubara, L & Guarda, E 1992, 'Pathologic hypertrophy with fibrosis: The structural basis for myocardial failure', Blood Pressure, vol. 1, no. 2, pp. 75-85. https://doi.org/10.3109/08037059209077497
Weber, Karl ; Brilla, Christian G. ; Campbell, Scott E. ; Zhou, Guoping ; Matsubara, Luiz ; Guarda, Eduardo. / Pathologic hypertrophy with fibrosis : The structural basis for myocardial failure. In: Blood Pressure. 1992 ; Vol. 1, No. 2. pp. 75-85.
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