Aims: The aim of the present study was to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after Ischemia/Reperfusion (I/R) exposure and the related mechanisms involved.
Methods and Results: Rats were subjected to Left Anterior Descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats, (Serca2aTG) rats, compared to Wild Type (WT) rats. Serca2aTG rats developed a significantly smaller myocardial infarction size compared to those in WT group. The expression of the Bcl-2 was lower in Serca2aTG rats compared with WT rats; but, Bcl-2 expression was markedly increased in Serca2aTG rats compared with WT after I/R. In addition, Bax was markedly downregulated in Serca2aTG rats compared to WT group after I/R. Meanwhile, autophagy marker LC-3B was increased in Serca2aTG group, and p62 was only increased in WT group but not in Serca2aTG group in response to I/R. Electron microscope observation confirmed that there were more autophagosomes in Serca2aTG group than in WT rats after I/R.
Conclusion: our findings demonstrated that the overexpression of Serca2a plays an important role in myocardial protection from I/R injury and postischemic functional recovery, which may be via antinecrotic, anti-apoptotic and pro-autophagy signal pathways. Our research provides solid basic data and new perspective on clinical treatment in heart failure patients with long-term over-expression of Serca2a.
Keywords: Cardiac protection, Ischemia-reperfusion(I/R), Sarcoplasmic reticulum Ca2+-ATPase (Serca2a), Apoptosis, Autophagy.
Strategies to Avoid TAVI-related Acute Kidney Injury
Current Pharmaceutical Design Development of Novel Cardiovascular Therapeutics From Small Regulatory RNA Molecules - An Outline of Key Requirements
Current Pharmaceutical Design Proteomics Analysis Revealed an Altered Left Ventricle Protein Profile in a Mouse Model of Transverse Aortic Constriction
Protein & Peptide Letters Heart Failure in East Asia
Current Cardiology Reviews Current Strategies to Achieve Further Cardiac and Renal Protection through Enhanced Renin-Angiotensin-Aldosterone System Inhibition
Reviews on Recent Clinical Trials A Comparative Summary on Antioxidant-like Actions of Timolol with Other Antioxidants in Diabetic Cardiomyopathy
Current Drug Delivery Anti-Inflammatory and Anti-Apoptotic Effects of Levosimendan in Decompensated Heart Failure: A Novel Mechanism of Drug-Induced Improvement in Contractile Performance of the Failing Heart
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Treatment of Hypertension in Heart Failure with Preserved Ejection Fraction
Current Hypertension Reviews Rational Autologous Cell Sources For Therapy of Heart Failure - Vehicles and Targets For Gene and RNA Therapies
Current Gene Therapy Left Ventricular Hypertrophy: A Shift in Paradigm
Current Medicinal Chemistry Aquaretic Agents: Whats Beyond the Treatment of Hyponatremia?
Current Pharmaceutical Design Humoral Immunity in Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets Polyphenols, Antioxidants and the Sympathetic Nervous System
Current Pharmaceutical Design Heart Failure Pharmacotherapy: Differences Between Adult and Paediatric Patients
Current Medicinal Chemistry Specificity of Three Vasopressin Receptor Antagonists
Letters in Drug Design & Discovery Cardiac Metabolism in Diabetes Mellitus
Current Pharmaceutical Design Hypertensive Heart Disease and the Role of Aldosterone Antagonists
Current Hypertension Reviews Stem Cell Therapy for the Treatment of Myocardial Infarction
Current Pharmaceutical Design Oxidative Stress During Myocardial Ischaemia and Heart Failure
Current Pharmaceutical Design Promises and Challenges of Adult Stem Cells in Cancer Therapy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)