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

Abstract

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 ΔΨm 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.

Through the Cat-Map Gateway: A Brief History of Cataract Genetics

“…RNLS: A truncation (deletion/insertion) variant in the gene for renalase ( RNLS ) on chromosome 10q was first identified in an Arab family with autosomal recessive congenital cataract [ 131 ]. RNLS functions as a secreted flavin adenine dinucleotide (FAD)-dependent monoamine oxidase involved in catecholamine metabolism and may play a role in mitigating mitochondrial dysfunction [ 132 ].…”

Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

“…This initial stage of apoptosis is potentially reversible by preventing the externalization of membrane PS residues [277,[282][283][284][285] to block inflammatory cells from detecting and removing injured cells that may remain functional [76,[286][287][288][289]. If the second phase of apoptotic cell death is reached, it is usually not reversible and involves the degradation of nuclear deoxyribonucleic acid (DNA) [136,137,167,169,[290][291][292][293][294]. The second stage of apoptosis consists of mitochondrial membrane depolarization, cytochrome c release, and caspase activation [136,193,252,290,[295][296][297][298][299][300].…”

“…In particular, microglia are important for removing damaged cells during membrane PS externalization and apoptosis [106,131,145,277,278,298,308,[324][325][326][327]]. Yet, microglia can lead to the generation of oxidative stress through the production of ROS [8,165,167,246,250,[328][329][330][331], which can require modulation by non-coding RNAs [251,[332][333][334][335][336], Wnt signaling [27,28,106,115,276,[337][338][339], and trophic factor pathways with erythropoietin (EPO) [27,[340][341][342][343][344][345][346]. In other scenarios, microglial cells can be helpful for protection during amyotrophic lateral sclerosis [347], remove brain amyloid [348,349], and preserve cholesterol homeostasis with autophagy …”

The Antioxidant Properties of Glucosinolates in Cardiac Cells Are Independent of H2S Signaling

“…), and genetic factors [17,18]. Cardiomyocytes are extremely vulnerable to oxidative stress and have limited regenerative capacity [19,20]. A large amount of evidence has shown that both GSLs and H 2 S have cardio-protective effects.…”