Role of apoptosis in cardiovascular disease

Apoptosis (2009) 14:536548 DOI 10.1007/s10495-008-0302-x

CELL DEATH AND DISEASE

Role of apoptosis in cardiovascular disease

Youngil Lee sa B. Gustafsson

Published online: 14 January 2009 Springer Science+Business Media, LLC 2009

Abstract Apoptosis plays a key role in the pathogenesis in a variety of cardiovascular diseases due to loss of terminally differentiated cardiac myocytes. Cardiac myocytes undergoing apoptosis have been identied in tissue samples from patients suffering from myocardial infarction, diabetic cardiomyopathy, and end-stage congestive heart failure. Apoptosis is a highly regulated program of cell death and can be mediated by death receptors in the plasma membrane, as well as the mitochondria and the endoplasmic reticulum. The cell death program is activated in cardiac myocytes by various stressors including cytokines, increased oxidative stress and DNA damage. Many studies have demonstrated that inhibition of apoptosis is cardio-protective and can prevent the development of heart failure. This review provides a current overview of the evidence of apoptosis in cardiovascular diseases and discusses the molecular pathways involved in cardiac myocyte apoptosis.

Keywords Apoptosis Heart failure Death receptors

Mitochondria Bcl-2

Introduction

Cardiovascular disease is the leading cause of morbidity and mortality in the developed world. A multitude of recent studies suggest that loss of terminally differentiated cardiac myocytes contributes to development of heart failure. There are three morphologically and biochemically distinct

forms of cell death that occur in the heart; necrosis, apoptosis, and possibly autophagy. Autophagy is a cellular process that degrades long lived proteins and dysfunctional organelles [1]. Autophagy is characterized by sequestration of cytoplasm in double-membrane vesicles called auto-phagosomes. Autophagosomes subsequently fuse with lysosomes, leading to degradation of their content [1]. This process is important for cellular homeostasis, and is a survival response upregulated in response to stress or starvation. However, excess autophagy can lead to cell death due to excessive digestion of organelles and essential proteins [2]. Necrosis is a passive form of cell death caused by ATP depletion and rapid disruption of cell membrane integrity resulting in spillage of intracellular contents into interstitial and extracellular space, which initiates inammation and induces damage to neighboring cells [3, 4]. In contrast, apoptosis is an energy requiring form of programmed cell death whereby damaged cells are removed without provoking inammation. Apoptosis is characterized by chromatin condensation, DNA fragmentation,...