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Renalase, a new secretory enzyme: Its role in hypertensive-ischemic cardiovascular diseases.

ABSTRACT: Abstract Renalase, a novel amine oxidase, is mainly expressed in the kidney, heart, and skeletal muscle. It has been known to degrade circulating catecholamines and plays a crucial role in human diseases. Recent studies have demonstrated its structure, unique bioactivities, function, and the gene polymorphisms in human diseases. In this review, we summarize the effects of renalase on hypertension, myocardial ischemia, acute kidney injury (AKI), ischemic stroke, cardiac dysfunction, organ transplantation, and diabetes mellitus reported in numerous studies.

SUBMITTER: Li X

PROVIDER: S-EPMC4005863 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Renalase, a new secretory enzyme: Its role in hypertensive-ischemic cardiovascular diseases.

Li Xiaogang X Huang Ruixia R Xie Zijian Z Lin Mingyuan M Liang Zhongshu Z Yang Yan Y Jiang Weihong W

Medical science monitor : international medical journal of experimental and clinical research 20140425

Abstract Renalase, a novel amine oxidase, is mainly expressed in the kidney, heart, and skeletal muscle. It has been known to degrade circulating catecholamines and plays a crucial role in human diseases. Recent studies have demonstrated its structure, unique bioactivities, function, and the gene polymorphisms in human diseases. In this review, we summarize the effects of renalase on hypertension, myocardial ischemia, acute kidney injury (AKI), ischemic stroke, cardiac dysfunction, organ transpl ...[more]

PMID: 24762661

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Project description:Overlapping risks for cancer and cardiovascular diseases (CVD), the two leading causes of mortality worldwide, suggest a shared biology between these diseases. The role of senescence in the development of cancer and CVD has been established. However, its role as the intersection between these diseases remains unclear. Senescence was originally characterized by an irreversible cell cycle arrest after a high number of divisions, namely replicative senescence (RS). However, it is becoming clear that senescence can also be instigated by cellular stress, so-called stress-induced premature senescence (SIPS). Telomere shortening is a hallmark of RS. The contribution of telomere DNA damage and subsequent DNA damage response/repair to SIPS has also been suggested. Although cellular senescence can mediate cell cycle arrest, senescent cells can also remain metabolically active and secrete cytokines, chemokines, growth factors, and reactive oxygen species (ROS), so-called senescence-associated secretory phenotype (SASP). The involvement of SASP in both cancer and CVD has been established. In patients with cancer or CVD, SASP is induced by various stressors including cancer treatments, pro-inflammatory cytokines, and ROS. Therefore, SASP can be the intersection between cancer and CVD. Importantly, the conventional concept of senescence as the mediator of cell cycle arrest has been challenged, as it was recently reported that chemotherapy-induced senescence can reprogram senescent cancer cells to acquire “stemness” (SAS: senescence-associated stemness). SAS allows senescent cancer cells to escape cell cycle arrest with strongly enhanced clonogenic growth capacity. SAS supports senescent cells to promote both cancer and CVD, particularly in highly stressful conditions such as cancer treatments, myocardial infarction, and heart failure. As therapeutic advances have increased overlapping risk factors for cancer and CVD, to further understand their interaction may provide better prevention, earlier detection, and safer treatment. Thus, it is critical to study the mechanisms by which these senescence pathways (SAS/SASP) are induced and regulated in both cancer and CVD.

Project description:Hypertension in elderly patients is one of the main problems in cardiovascular diseases. The sympathetic nervous system hyperactivity seen in older patients is a known risk factor for hypertension and other cardiovascular events as well as chronic kidney disease. Renalase, secreted by the kidney and circulated in blood, may regulate the sympathetic tone by catecholamine degradation and in this way has an impact on cardiovascular and renal complications.To assess the impact of age on renalase and catecholamine concentration in hypertensive patients, including those on dialyses and its possible relation to blood pressure control and cardiovascular disease.The study cohort of 211 patients was divided into two groups according to age below 65 years (range 19-64) and above 65 years (range 65-86). The older group represented 38% of the whole studied population and 75% of them were dialyzed. The two groups of different ages were also divided into dialysis and nondialysis subgroups. The serum renalase, dopamine, and norepinephrine concentration together with blood pressure value and echocardiography were assessed.Patients aged 65 years and more had higher renalase (20.59 vs 13.14 µg/mL, P=0.02) and dopamine (41.71 vs 15.46 pg/mL, P<0.001) concentration as well as lower diastolic blood pressure (75.33 vs 85 mmHg, P=0.001), advanced abnormalities in echocardiography, and more often suffered from diabetes and coronary artery disease. The significant correlation between age and renalase (r=0.16; P=0.019), norepinephrine (r=0.179; P=0.013), and dopamine (r=0.21; P=0.003) was found in the whole study population. In the nondialysis subgroup, 44% had chronic kidney disease, mostly in the stage 2 (83%). There was a significantly higher norepinephrine concentration (1.21 vs 0.87 ng/mL; P=0.008) in older patients of that population. In the dialysis subgroup, there were no differences between renalase and catecholamine level but older participants had lower diastolic blood pressure (69 vs 78 mmHg, P=0.001) and ejection fraction (51% vs 56.8%, P=0.03).The elevated renalase level in older hypertensive patients is related rather to kidney function and cardiovascular diseases than to age itself. Thus, renalase appears to be the possible new marker of these indications in this special population.

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Renalase, a new secretory enzyme: Its role in hypertensive-ischemic cardiovascular diseases.

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Renalase, a new secretory enzyme: Its role in hypertensive-ischemic cardiovascular diseases.

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