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(Hypertension. 2001;38:1406.)
© 2001 American Heart Association, Inc.

Fourth International Seminar on Cardiovascular Biology and Medicine: Part II

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

Mechanisms and Potential Management

Maria Antonia Fortuño; Susana Ravassa; Ana Fortuño; Guillermo Zalba; Javier Díez

From the Division of Cardiovascular Pathophysiology, School of Medicine (M.A.F., S.R., A.F., G.Z., J.D.), and the Department of Cardiology and Cardiovascular Surgery, University Clinic (J.D.), University of Navarra, Pamplona, Spain.

Correspondence to Maria Antonia Fortuño Cebamanos, PhD, Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, C/Irunlarrea, 1, 31008 Pamplona, Spain. E-mail fortuto{at}unav.es

Abstract

Hypertensive heart disease is a progressive condition in which the compensatory left ventricular hypertrophy that maintains cardiac output leads to myocardial remodeling, characterized by fibrosis, insufficient vascularization, and alterations in cardiomyocytes, including contractile disturbances, changes in gene expression, and decrease in the number of cells. Structural abnormalities in the myocardial wall accelerate the development of diastolic and systolic dysfunction, resulting in heart failure. Many observations point to the apoptotic cell death of cardiomyocytes as a relevant factor in the transition from compensatory hypertrophy to pump failure in experimental and human hypertension. Potential inducers of cardiomyocyte apoptosis in overloaded hearts include extrinsic factors, such as mechanical forces, neurohormonal activation, oxidative stress, hypoxia, and cytokines. Some lines of evidence indicate that angiotensin II and the overstretching of cardiomyocytes are originally involved in the triggering of apoptosis in hypertension, whereas other factors are being investigated. Furthermore, intracellular changes, such as downregulation of survival proteins or activation of death proteins, seem to play an important role. The assumption that the apoptosis of cardiomyocytes worsens hypertensive heart disease prognosis brings forth new approaches to avoid or slow the transition to pump failure. In this respect, experimental data indicate that currently used antihypertensive drugs interfere with cardiomyocyte apoptosis. Moreover, the knowledge of intracellular apoptotic processes in cardiomyocytes provides novel therapeutic strategies to be added to the multimodal approach in the prevention of heart failure.

Key Words: angiotensin II • apoptosis • myocytes • hypertension, arterial • cardiomyopathies

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