title: Mechanisms involved in attenuated cardio-protective role of ischemic preconditioning in metabolic disorders.
abstract: Myocardial infarction is a pathological state which occurs due to severe abrogation of the blood supply (ischemia) to a part of heart, which can cause myocardial damage. The short intermittent cycles of sub-lethal ischemia and reperfusion has shown to improve the tolerance of the myocardium against subsequent prolonged ischemia/reperfusion (I/R)-induced injury, which is known as ischemic preconditioning (IPC). Although, IPC-induced cardioprotection is well demonstrated in various species, including human beings, accumulated evidence clearly suggests critical abrogation of the beneficial effects of IPC in diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. Various factors are involved in the attenuation of the cardioprotective effect of preconditioning, such as the reduced release of calcitonin gene-related peptide (CGRP), the over-expression of glycogen synthase kinase-3β (GSK-3β) and phosphatase and tensin homolog (PTEN), impairment of mito-KATP channels, the consequent opening of mitochondrial permeability transition pore (MPTP), etc. In this review, we have critically discussed the various signaling pathways involved in abrogated preconditioning in chronic diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. We have also focused on the involvement of PTEN in abrogated preconditioning and the significance of PTEN inhibitors.
authors.affiliation: Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: A
authors.initials: A
authors.lastname: Rana
authors.affiliation: Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: N
authors.initials: N
authors.lastname: Goyal
authors.affiliation: Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: A
authors.initials: A
authors.lastname: Ahlawat
authors.affiliation: Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: S
authors.initials: S
authors.lastname: Jamwal
authors.affiliation: Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: B V K
authors.initials: BV
authors.lastname: Reddy
authors.affiliation: Cardiovascular Division, Department of Pharmacology, I.S.F College of Pharmacy, Moga-142001, Punjab, India ssm.research@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
mesh_terms: D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008659:Metabolic Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009124:Muscle Proteins; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D009124:Muscle Proteins
keywords: PI3K/Akt pathway; PTEN; diabetic myocardium; glycogen synthase kinase-3β; hyperlipidemic myocardium; ischemic preconditioning