Fibrosis in hypertensive heart disease

Molecular pathways and cardioprotective strategies

Atta U. Shahbaz, Yao Sun, Syamal Bhattacharya, Robert A. Ahokas, Ivan Gerling, Jesse E. McGee, Karl Weber

Research output: Contribution to journalReview article

38 Citations (Scopus)

Abstract

Fibrosis is a fundamental component of the adverse structural remodelling of myocardium found in hypertensive heart disease (HHD). A replacement fibrosis appears at sites of previous cardiomyocyte necrosis to preserve the structural integrity of the myocardium. Such scarring has adverse functional consequences. The extensive distribution of fibrosis involving the right and left heart suggests cardiomyocyte necrosis is widespread. Together, the loss of these contractile elements and fibrous tissue deposition in the form of stiff in-series and in-parallel elastic elements contribute to the progressive failure of this normally efficient muscular pump. Pathogenic mechanisms modulating fibrous tissue formation at sites of repair include auto/paracrine properties of locally generated angiotensin II and endothelin-1. This study focuses on the signal-transducer-effector pathway involved in cardiomyocyte necrosis and the crucial pathogenic role of intracellular calcium overloading, and the subsequent induction of oxidative stress originating within its mitochondria that dictates the opening of the mitochondrial permeability transition pore. The ensuing osmotic destruction of these organelles is followed by necrotic cell death. It is now further recognized that calcium overloading of cardiac myocytes and mitochondria functioning as pro-oxidant is pathophysiologically counterbalanced by an intrinsically coupled zinc entry, which serves as an antioxidant. The prospect of raising intracellular zinc by adjuvant nutriceutical supplementation can, therefore, be preferentially exploited to uncouple this intrinsically coupled calcium-zinc dyshomeostasis in favour of endogenous antioxidant defences. Novel cardioprotective strategies may thus be at hand and deserve to be explored further in the overall management of patients with HHD.

Original languageEnglish (US)
JournalJournal of Hypertension
Volume28
Issue numberSUPPL. 1
DOIs
StatePublished - Sep 1 2010

Fingerprint

Cardiac Myocytes
Heart Diseases
Fibrosis
Zinc
Necrosis
Calcium
Myocardium
Mitochondria
Antioxidants
Endothelin-1
Dietary Supplements
Transducers
Angiotensin II
Organelles
Cicatrix
Reactive Oxygen Species
Oxidative Stress
Cell Death
Hand

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Fibrosis in hypertensive heart disease : Molecular pathways and cardioprotective strategies. / Shahbaz, Atta U.; Sun, Yao; Bhattacharya, Syamal; Ahokas, Robert A.; Gerling, Ivan; McGee, Jesse E.; Weber, Karl.

In: Journal of Hypertension, Vol. 28, No. SUPPL. 1, 01.09.2010.

Research output: Contribution to journalReview article

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