Cardioprotection in right heart failure

Abstract

Ischaemic and pharmacological conditioning of the left ventricle is mediated by the activation of signalling cascades, which finally converge at the mitochondria and reduce ischaemia/reperfusion (I/R) injury. Whereas the molecular mechanisms of conditioning in the left ventricle are well characterized, cardioprotection of the right ventricle is principally feasible but less established. Similar to what is known for the left ventricle, a dysregulation in signalling pathways seems to play a role in I/R injury of the healthy and failing right ventricle and in the ability/inability of the right ventricle to respond to a conditioning stimulus. The maintenance of mitochondrial function seems to be crucial in both ventricles to reduce I/R injury. As far as currently known, similar molecular mechanisms mediate ischaemic and pharmacological preconditioning in the left and right ventricles. However, the two ventricles seem to respond differently towards exercise‐induced preconditioning.LINKED ARTICLESThis article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc

Mitochondrial Monoamine Oxidase: Another Player in Pulmonary Hypertension?

“…In contrast to the right ventricle, the relevance of MAO-A inhibition for left ventricular pressure overload–induced heart failure and other left ventricular pathologies was previously shown in various experimental models ( 10 ). This study thus fills the gap between the right and left ventricles and provides more evidence that the right and left heart respond differently to pressure overload, as suggested by previous studies regarding the source of ROS and antioxidant defense mechanisms in right and left heart hypertrophy and failure ( 2 , 11 , 12 ). Moreover, this study adds another piece to the puzzle to understand the multifactorial pathogenesis of PH, and it supports previous findings that increased ROS contribute to pulmonary vascular remodeling.…”

Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study)

“…There are now thousands of studies which reported >100 different signaling molecules and mechanisms of conditioning in a wide range of experimental preparations, from isolated subcellular structures to isolated cardiomyocytes with exposure to hypoxia/reoxygenation, from cultured cardiomyoblast cell lines to freshly isolated neonatal or adult cardiomyocytes, from buffer-perfused isolated hearts with global or regional ischemia and reperfusion to in vivo and in situ preparations with coronary artery occlusion and reperfusion, using different methodologies from biochemical to immunoblotting techniques [ 42 ]. Intensive research has been performed to elucidate the signalling pathways, which become activated upon a conditioning stimulus [ 43 ]. The protein kinase B, endothelial nitric oxygen synthase, glycogen synthase kinase 3b, p44/42, and signal transducer and activator of transcription 3 may be considered as indicators of the intracellular changes taking place during remote ischemic conditioning.…”

The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases

“…4 ). 44 , 45 Mitophagy regulates both mitochondrial quantity and quality in vivo in response to hypoxia or hypoxic conditions especially I/R heart injury in both platelets and cardiomyocytes. It was further suggested that monitoring mitochondrial quality and mitochondrial functional status of platelets offered useful and convenient approach before the application of ischemic and pharmacological preconditioning, providing a new strategy to protect cardiac function and fight cardiovascular diseases.…”