Molecular mechanisms mediating preconditioning following chronic ischemia differ from those in classical second window
Year: 2010
Type: article
Abstract: A major difference between experimental ischemic preconditioning (IPC), induced by brief ischemic episodes, and the clinical situation is that patients generally have repetitive episodes of ischemia. We used a swine model to examine differences in genes regulated by classical second-window IPC (SWOP) [two 10-min episodes of coronary artery occlusion (CAO) followed by 24 h reperfusion] compared with repetitive CAO/reperfusion (RCO), i.e., two 10-min CAO 12 h apart, and to repetitive coronary stenosis (RCS), six episodes of 90 min coronary stenosis 12 h apart (n = 5/group). All three models reduced infarct size by 60-85%, which was mediated by nitric oxide in SWOP but not in the other two models. We employed microarray analyses to discover additional molecular pathways intrinsic to models of repetitive ischemia and different from classical SWOP. There was an 85% homology in gene response between the RCO and RCS models, whereas SWOP was qualitatively different. Both RCO and RCS, but not SWOP, showed downregulation of genes encoding proteins involved in oxidative metabolism and upregulation of genes involved in protein synthesis, unfolded protein response, autophagy, heat shock response, protein secretion, and an activation of the NF-kappaB signaling pathway. Therefore, the regulated genes mediating IPC with repetitive ischemia differ radically from SWOP both quantitatively and qualitatively, showing that a repetitive pattern of ischemia, rather than the difference between no-flow vs. low-flow ischemia, dictates the genomic response of the heart. These findings illustrate new cardioprotective mechanisms developed by repetitive IPC, which are potentially more relevant to patients with chronic ischemic heart disease, who are subjected to repetitive episodes of ischemia.
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1311753952, Age and Gender Differences in Apoptosis and Stem Cells, G2026374743, G2272290945, Aging Effects on Cardiovascular Function, Integrative Mechanisms in Cardiovascular Disease, G2818757314, G2824958676, Longevity and Stress Resistance, G3475925159, Myocardial Hypertrophy and Heart Failure, G567741145, Rescue of Beta-Adrenergic Cardiomyopathy by Inhibition of Adenylyl Cyclase, Intrinsic Vascular Smooth Muscle Cell Stiffness, Cardiovascular Control in Normal and Disease States, Mechanisms of myocardial ischemia and reperfusion, G7639128960, Adenylyl cyclase isoforms in hypertrophy and heart failure
OpenAlex ID: W2119660342