Apoptosis and oncosis in acute coronary syndromes: Assessment and implications

Abstract

The rational design of therapeutic interventions for protection of ischemic myocardium from ultimate death requires an understanding of the mechanistic basis of cardiomyocyte (CM) cell death, its timing and the tools for its quantification. Until recently, CM cell death following ischemia and/or reperfusion was considered to involve necrosis or 'accidental cell death' from very early on. Collective evidence over the past decade indicates that early CM cell death after myocardial ischemia and post-ischemic reperfusion involves apoptosis with cell shrinkage and drop-out, and/or oncosis with cell swelling followed by necrosis. This paradigm shift suggests that different approaches for cardioprotection are required. Oncologists, pathologists, anatomists and basic scientists who have studied apoptosis over the last three decades separated physiological apoptosis from inappropriate apoptosis in pathological states. Until recently, cardiologists resisted the concepts of CM apoptosis and regeneration. Cumulative evidence indicating that apoptosis in the heart may occur in different cell types, spread from one cell type to another, and occur in bursts, may have profound implications for therapies aimed at protection of ischemic myocardium by targeting CM apoptosis in acute coronary syndromes. This review focuses on a critique of the methods used for the assessment of CM apoptosis and the implications of CM apoptosis in acute coronary syndromes.

Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis

“…Since the conception of apoptosis was proposed by Kerr in 1972 [11] , apoptosis has been extensively studied. In recent years, attention has been paid to another cell death pathwayoncosis, and it was gradually realized that oncosis makes no less sense than apoptosis [12] . Oncosis has a feature of cell swelling, and cell membrane integrity is destroyed and DNA is split into non-specific fragments.…”

Rho kinase in the regulation of cell death and survival

“…Apoptosis is a controlled, energy-dependent active form of cell death characterized by morphological changes such as shrinkage of the cell, condensation of chromatin and disintegration of the cell into small fragments that can be removed by phagocytosis [19]. Necrosis is an uncontrolled, energyindependent process characterized by cellular edema and disruption of the plasma membrane, leading to release of the cellular components and inflammatory tissue response [57]. Autophagy is characterized by sequestration of bulk cytoplasm and organelles in double or multi-membrane autophagic vesicles and their delivery to and subsequent degradation by cell's own lysosomal system [124].…”

Mitochondria: A mirror into cellular dysfunction in heart disease

“…Bid and Bik), which facilitate cytochrome c release, whereas anti-apoptotic proteins Bcl-2 and Bcl-X L prevent the release of cytochrome c [169][170][171][172][173][174][175]. Occurring rapidly, the release of mitochondrial apoptotic factors, in particular cytochrome c, functions to activate caspase 2 [176] and caspase 9 (as reviewed in [177]), which in turn activate the effector caspases, in particular caspase 3 to produce the apoptotic phenotype. Anti-apoptotic members of the Bcl-2 family, including Bcl-2 and Bcl-X L , are required for continuing function of cardiomyocytes.…”

“…Linking the OMM and IMM, the MPTP is suggested to result in the dissipation of the mitochondrial membrane potential (Dc M ) when open [182], with downstream effects on mitochondrial depolarization, uncoupling, swelling and outer membrane rupture (as reviewed in [177]). Conditions of oxidative stress and Ca 21 overload promote the opening of the MPTP [183,184].…”