Abstract
ObjectiveRenalase, a novel secretory flavoprotein with amine oxidase activity, is secreted into the blood by the kidneys and is hypothesized to participate in blood pressure (BP) regulation. We investigated the associations of renalase with BP and the risk of hypertension by examining renalase single nucleopeptide polymorphism (SNPs), serum renalase levels, and renal expression of renalase in humans.Methods① Subjects (n = 514) from the original Baoji Salt-Sensitive Study cohort were genotyped to investigate the association of renalase SNPs with longitudinal BP changes and the risk of hypertension during 14 years of follow-up. ② Two thousand three hundred and ninety two participants from the Hanzhong Adolescent Hypertension Study cohort were used to examine the association of serum renalase levels with hypertension. Renalase expression in renal biopsy specimens from 193 patients were measured by immunohistochemistry. ③ Renalase expression was compared in hypertensive vs. normotensive patients.Results① SNP rs7922058 was associated with 14-year change in systolic BP, and rs10887800, rs796945, rs1935582, rs2296545, and rs2576178 were significantly associated with 14-year change in diastolic BP while rs1935582 and rs2576178 were associated with mean arterial pressure change over 14 years. In addition, SNPs rs796945, rs1935582, and rs2576178 were significantly associated with hypertension incidence. Gene-based analysis found that renalase gene was significantly associated with hypertension incidence over 14-year follow-up after adjustment for multiple measurements. ② Hypertensive subjects had higher serum renalase levels than normotensive subjects (27.2 ± 0.4 vs. 25.1 ± 0.2 μg/mL). Serum renalase levels and BPs showed a linear correlation. In addition, serum renalase was significantly associated with the risk of hypertension [OR = 1.018 (1.006–1.030)]. ③ The expression of renalase in human renal biopsy specimens significantly decreased in hypertensive patients compared to non-hypertensive patients (0.030 ± 0.001 vs. 0.038 ± 0.004).ConclusionsThese findings indicate that renalase may play an important role in BP progression and development of hypertension.
Highlights
Hypertension is one of the most common diseases, and is a major risk factor for cardiovascular and cerebrovascular diseases and chronic kidney disease (CKD) [1]
During 14 years of follow-up, average SBP, DBP, and mean arterial pressure (MAP) increased by 21.2, 7.9, and 12.3 mmHg, respectively, and 160 (53.9%) subjects who were normotensive at baseline developed hypertension (Table 1)
To the best of our knowledge, this is the first study to investigate the associations of RNLS gene with blood pressure (BP) levels, longitudinal BP changes and hypertension incidence in a Chinese cohort
Summary
Hypertension is one of the most common diseases, and is a major risk factor for cardiovascular and cerebrovascular diseases and chronic kidney disease (CKD) [1]. Several studies have shown that sympathetic over-activity is crucial in the pathogenesis of hypertension, and interventions of sympathetic deactivation have been shown to lower BP levels [2]. Firstly discovered in 2005, is a 342-amino-acid flavoprotein with monoamine oxidase activity. It is highly expressed in the kidneys and heart, and circulates in the blood to modulate cardiac function and BP [3, 4]. Serum renalase levels are higher in hypertensive than normotensive individuals [8, 9]. Schlaich et al [10] found that serum renalase was higher in normotensive controls than in patients with resistant hypertension. The correlation between serum and kidney renalase in hypertensive patients needs to be further clarified
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