title: High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms.
abstract: Ischemic injury is associated with acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting and open heart surgery. The timely re-establishment of blood flow is critical in order to minimize cardiac complications. Reperfusion after a prolonged ischemic period, however, can induce severe cardiomyocyte dysfunction with mitochondria serving as a major target of ischemia/reperfusion (I/R) injury. An increase in the formation of reactive oxygen species (ROS) induces damage to mitochondrial respiratory complexes leading to uncoupling of oxidative phosphorylation. Mitochondrial membrane perturbations also contribute to calcium overload, opening of the mitochondrial permeability transition pore (mPTP) and the release of apoptotic mediators into the cytoplasm. Clinical and experimental studies show that ischemic preconditioning (ICPRE) and postconditioning (ICPOST) attenuate mitochondrial injury and improve cardiac function in the context of I/R injury. This is achieved by the activation of two principal cell survival cascades: 1) the Reperfusion Injury Salvage Kinase (RISK) pathway; and 2) the Survivor Activating Factor Enhancement (SAFE) pathway. Recent data suggest that high density lipoprotein (HDL) mimics the effects of conditioning protocols and attenuates myocardial I/R injury via activation of the RISK and SAFE signaling cascades. In this review, we discuss the roles of apolipoproteinA-I (apoA-I), the major protein constituent of HDL, and sphingosine 1-phosphate (S1P), a lysosphingolipid associated with small, dense HDL particles as mediators of cardiomyocyte survival. Both apoA-I and S1P exert an infarct-sparing effect by preventing ROS-dependent injury and inhibiting the opening of the mPTP.
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: crwhite@uab.edu.
authors.forename: C Roger
authors.initials: CR
authors.lastname: White
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Giordano
authors.affiliation: The Division of Gerontology, Geriatric Medicine and Palliative Care, University of Alabama at Birmingham, Birmingham, AL, USA; Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
mesh_terms: D000818:Animals; D001343:Autophagy; D002470:Cell Survival; D004734:Energy Metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
chemical_list: D008075:Lipoproteins, HDL
keywords: ApoA-I; Hdl; Ischemia-reperfusion; Mitochondrion; Myocardium; Sphingosine 1-Phosphate