Renalase: a novel regulator of cardiometabolic and renal diseases

Vijayakumar, Anupama; Mahapatra, Nitish R.

doi:10.1038/s41440-022-00986-1

Cited by 11 publications

(5 citation statements)

References 107 publications

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“…In addition to its link to Li response in BP (Amare et al 2023 ), serum renalase levels have been reported to be lower in patients with schizophrenia (SCZ) than in control individuals (Catak et al 2019 ), and Li response was previously shown to inversely associate with the genetic risk for SCZ (Amare et al 201 8). RNLS is thought to modulate blood pressure and cardiac function, and has been associated with metabolic and cardiovascular alterations as well as kidney disease (Vijayakumar & Mahapatra 2022 ), all of which are affected by Li. Similar are the cases of CSMD2 and GRIN2A , which are involved in the control of the complement cascade and N-methyl-D-aspartate (NMDA) receptor activity, respectively.…”

Section: Discussionmentioning

confidence: 99%

Exploring the genetics of lithium response in bipolar disorders

Herrera-Rivero,

Adli,

Akiyama

et al. 2024

Int J Bipolar Disord

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Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

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Section: Discussionmentioning

confidence: 99%

Exploring the genetics of lithium response in bipolar disorders

Herrera-Rivero,

Adli,

Akiyama

et al. 2024

Int J Bipolar Disord

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“…Additionally, RNL is a cytokine that modulates the mitogen-activated protein kinase pathway leading to cytoprotective, anti-inflammatory, and antiapoptotic effects [reviewed in 59 ]. According to current knowledge, RNL might modulate blood pressure in animals and humans by influencing catecholamine metabolism, renal dopamine secretion, and renal sympathetic innervation [ 19 , 59 , 60 ]. For instance, the renalase-knockout mice showed increased systolic and diastolic blood pressure and increased catecholamine concentrations compared to the wild-type animals despite normal renal function [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, RNL is investigated mainly in the context of chronic kidney, cardiovascular and oncologic diseases [ 60 ], while the possible associations with reproductive disturbances are poorly explored. However, abundant RNL expression has been described in rodent ovaries and adrenal glands [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS

et al. 2023

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Purpose Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the sympathetic nervous system in the syndrome development, while human studies are still contradictory. The present study aims to investigate the possible influence of plasma-free metanephrine (MN), and normetanephrine (NMN), nerve growth factor (NGF), and renalase (RNL) on the hormonal and metabolic parameters in women with PCOS and healthy controls. Methods Fifty patients with PCOS and 30 healthy women participated in the study. The plasma-free MN and NMN, NGF, RNL, anti-Mullerian hormone (AMH), gonadotropin, androgen levels, and metabolic parameters were investigated. Results Plasma-free NMN and NGF concentrations were increased in PCOS individuals, while RNL levels were decreased compared to healthy volunteers. Increased plasma-free NMN (OR = 1.0213 [95%CI 1.0064–1.0364], p = 0.005) and NGF (OR = 1.0078 [95%CI 1.0001–1.0155], p = 0.046) but not MN or RNL levels were associated with a higher risk of PCOS after adjustment for age. Plasma-free NMN levels were positively associated with the LH ( r = +0.253; p = 0.039). androstenedione ( r = +0.265; p = 0.029), 17-OH progesterone ( r = +0.285; p = 0.024), NGF ( r = +0.320; p = 0.008), and AMH ( r = +0.417; p < 0.001) concentrations of the investigated women. RNL levels were inversely related to the BMI ( r = −0.245; p = 0.029), HOMA-IR ( r = −0.250; p = 0.030), free testosterone ( r = −0.303; p = 0.006) levels. systolic ( r = −0.294; p = 0.008) and diastolic ( r = −0.342; p = 0.002) blood pressure. Conclusions Increased sympathetic noradrenergic activity and NGF synthesis might be related to the increased AMH and delta-4 androgen levels in a subgroup of PCOS patients. RNL levels might influence the metabolic status of PCOS patients. Further studies are needed to explore the significance of adrenal medullar and autonomic dysfunction for developing different PCOS phenotypes and their subsequent cardiovascular complications.

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“…Finally, renalase can hinder inflammasome activation and the release of IL-1β [ 32 , 44 , 62 ]. Taken together, renalase favors significant cytoprotection related to inflammation, oxidative stress, and apoptosis [ 28 , 29 , 30 , 31 , 32 , 37 , 38 , 39 , 50 , 59 , 62 ], whereby recent research also discloses its potential in diverse cardiac [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ] and kidney pathologies [ 75 , 76 , 77 , 78 ] and in the pathophysiology of COVID-19 [ 79 , 80 ]. It will be captivating to conduct future scrutiny toward an excellent comprehension of renalase pleiotropy.…”

Section: The Molecular Signature Of Renalasementioning

confidence: 99%

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

Stojanović

Milenković

et al. 2023

Cells

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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.

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Renalase: a novel regulator of cardiometabolic and renal diseases

Cited by 11 publications

References 107 publications

Exploring the genetics of lithium response in bipolar disorders

Exploring the genetics of lithium response in bipolar disorders

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS

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

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