Moderate exercise training is a key aspect of primary and secondary prevention strategies. Shear-induced upregulation of eNOS activity and function in the vascular endothelium is considered as one of the main molecular mechanisms of exercise-induced protection against myocardial ischemia/ reperfusion (I/R) injury. It has been reported that levels of plasma nitrite, which are largely dependent on eNOS activity, were increased in healthy subjects after acute exercise, while this increase was abolished in coronary artery disease (CAD) patients. Our group and others demonstrated that RBCs contain a functional eNOS, which contributes to systemic nitrite homeostasis and to cardioprotection; moreover, expression and activity of red cell eNOS are decreased in CAD patients and significantly correlated with flow-mediated dilation, a diagnostic marker of endothelial function. Therefore, in addition to vascular eNOS, also red cell eNOS (or in more general terms NO metabolic activity of RBCs) may play a role in exercise-dependent changes of NO-bioavailability. In this review, we will focus on what is known and what is unknown about the role of RBCs in exercise-dependent cardioprotection with emphasis on RBC signaling and red cell eNOS. In detail, we will discuss the effects and molecular mechanisms of shear stress and exercise training on RBC signaling and function, review how these changes may influence blood rheology and systemic hemodynamics and highlight the potential role of red cell eNOS-mediated cardiovascular protection induced by physical activity against myocardial injury in animal and human studies and in clinical settings.
Keywords: eNOS, red blood cells, shear stress, exercise, ischemia/reperfusion, myocardial infarction, cardioprotection.
Is Atorvastatin Superior to Other Statins? Analysis of the Clinical Trials with Atorvastatin Having Cardiovascular Endpoints
Reviews on Recent Clinical Trials Effect of β-Blockers on Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery
Current Drug Targets The Prostaglandin Agonist Beraprost Aggravates Doxorubicin-mediated Apoptosis by Increasing iNOS Expression in Cardiomyocytes
Current Vascular Pharmacology Cardioprotective Utility of Urocortin in Myocardial Ischemia- Reperfusion Injury: Where do We Stand?
Current Molecular Pharmacology Traditional and Alternative Therapies for Refractory Angina
Current Pharmaceutical Design Circadian MicroRNAs in Cardioprotection
Current Pharmaceutical Design Pharmacological Approach of No-Reflow Phenomenon Related with Percutaneous Coronary Interventions
Cardiovascular & Hematological Agents in Medicinal Chemistry Assessment of Acute Coronary Syndromes: Focus on Novel Biomarkers
Current Medicinal Chemistry Would Polymorphic Variants of Dopamine-2 Receptor Gene (DRD2) and Serotonin Transporter Gene (SERT) be a Common Genetic Risk Factor for Comorbid Drug Abuse and Myocardial Ischemia? A Hypothesis- generating Study
Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) SIRT1 as a Promising Novel Therapeutic Target for Myocardial Ischemia Reperfusion Injury and Cardiometabolic Disease
Current Drug Targets The Coronary Collateral Circulation in Man
Current Cardiology Reviews Bradykinin is Involved in the Mediation of Cardiac Nociception during Ischemia through Upper Thoracic Spinal Neurons
Current Neurovascular Research The Role of Hydrogen Sulfide and H2S-donors in Myocardial Protection Against Ischemia/Reperfusion Injury
Current Medicinal Chemistry Renal Protective Effect of Metabolic Therapy in Patients with Coronary Artery Disease and Diabetes: From Bench to Bed Side
Current Pharmaceutical Design ATP-Sensitive K+ Channel Openers: Old Drugs with New Clinical Benefits for the Heart
Current Vascular Pharmacology The Meaning of Different Forms of Structural Myocardial Injury, Immune Response and Timing of Infarct Necrosis and Cardiac Repair
Current Vascular Pharmacology Effects of Metabolic Approach in Diabetic Patients with Coronary Artery Disease
Current Pharmaceutical Design Pre-Emptive Conditioning of the Ischemic Heart
Cardiovascular & Hematological Agents in Medicinal Chemistry Toll-Like Receptors and Myocardial Ischemia/Reperfusion, Inflammation, and Injury
Current Cardiology Reviews Insight to the Pathophysiology of Stable Angina Pectoris
Current Pharmaceutical Design