The Multi-Faceted Nature of Renalase for Mitochondrial Dysfunction Improvement in Cardiac Disease

The cellular mechanisms and signaling network that guide the cardiac disease pathophysiology are inextricably intertwined, which explains the current scarcity of effective therapy and to date remains the greatest challenge in state-of-the-art cardiovascular medicine. Accordingly, a novel concept has emerged in which cardiomyocytes are the centerpiece of therapeutic targeting, with dysregulated mitochondria as a critical point of intervention. Mitochondrial dysfunction pluralism seeks a multi-faceted molecule, such as renalase, to simultaneously combat the pathophysiologic heterogeneity of mitochondria-induced cardiomyocyte injury. This review provides some original perspectives and, for the first time, discusses the functionality spectrum of renalase for mitochondrial dysfunction improvement within cardiac disease, including its ability to preserve mitochondrial integrity and dynamics by suppressing mitochondrial & UDelta;& psi;m collapse; overall ATP content amelioration; a rise of mtDNA copy numbers; upregulation of mitochondrial genes involved in oxidative phosphorylation and cellular vitality promotion; mitochondrial fission inhibition; NAD(+) supplementation; sirtuin upregulation; and anti-oxidant, anti-apoptotic, and anti-inflammatory traits. If verified that renalase, due to its multi-faceted nature, behaves like the guardian of mitochondria by thwarting pernicious mitochondrial dysfunction effects and exerting therapeutic potential to target mitochondrial abnormalities in failing hearts, it may provide large-scale benefits for cardiac disease patients, regardless of the underlying causes.

Automated summary

The cellular mechanisms and signaling network underlying cardiac disease are complex, leading to the current lack of effective therapy. Cardiomyocytes and mitochondrial dysfunction have emerged as key targets for intervention. This review explores the potential of renalase to improve mitochondrial dysfunction in cardiac disease through multiple mechanisms, including preserving mitochondrial integrity and dynamics, increasing ATP content, enhancing mtDNA copy numbers, upregulating mitochondrial genes, inhibiting mitochondrial fission, supplementing NAD(+), upregulating sirtuins, and exerting antioxidant, anti-apoptotic, and anti-inflammatory effects.