Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications.
Highlights
The heart is an organ with limited capacity for regeneration and repair; it is susceptible to numerous stresses and must respond to these insults in order to adapt to everchanging workload demands
The available evidence is consistent that autophagy is protective under conditions of mild-to-moderate ischemia, the same cannot be said of autophagy elicited by reperfusion
Activation of AMPK by metformin blunted development of heart failure (HF) induced by myocardial infarction (MI), and inhibiting mammalian target of rapamycin (mTOR) led to reduced remodeling and improved cardiac function after MI.[13]
Summary
The heart is an organ with limited capacity for regeneration and repair; it is susceptible to numerous stresses and must respond to these insults in order to adapt to everchanging workload demands. Autophagy is upregulated further, even though the delivery of oxygen and nutrients is restored and AMPK is rapidly inactivated.[5,10] The continued activation of autophagy during reperfusion is qualitatively different than that in ischemia, especially in terms of mechanisms of induction Stimulators, such as oxidative stress, mitochondrial damage/BNIP3, endoplasmic reticulum stress, and calcium overload, likely have more important roles in maintaining autophagy at a higher level during reperfusion.[11] the available evidence is consistent that autophagy is protective under conditions of mild-to-moderate ischemia, the same cannot be said of autophagy elicited by reperfusion. Ischemia induces a decline in the levels of LAMP2, a protein critical for autophagosome–lysosome fusion, mediated by ROS-induced activation of serine and cysteine proteases; reperfusion induces upregulation of Beclin 1, which further impairs autophagosome processing, culminating in increased ROS generation, mitochondrial permeabilization, and cardiomyocyte death.[12] More investigation is needed to clarify when and how elevated autophagy may be pro-survival to cardiac myocytes subjected to reperfusion injury
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
