Abstract
Vasohibin-1 (VASH-1) is a negative feedback regulator of angiogenesis, and a small vasohibin-binding protein (SVBP) serves as its secretory chaperone and contributes to its antiangiogenic effects. In the present study, we aimed to define the clinical significance of VASH-1 and SVBP in patients with chronic kidney disease (CKD). We recruited 67 Japanese hospitalized patients with renal disorders with (n = 45) or without (n = 22) renal biopsy samples and 10 Japanese healthy controls. We evaluated the correlations between the plasma and urinary levels of VASH-1/VASH-1-SVBP complex/SVBP and the clinicopathological parameters. The plasma levels of VASH-1 were inversely correlated with age and systolic and diastolic blood pressure and positively correlated with crescent formation. Increased plasma and urinary levels of VASH-1 and VASH-1-SVBP complex were significantly correlated with worse renal outcomes. These results demonstrate an association between elevated urinary and plasma levels of VASH-1 and progressive decline of the renal function, thus suggesting a potential role for VASH-1 in predicting a worse renal prognosis in patients with renal disease, including CKD.
Highlights
Chronic kidney disease (CKD) is associated with an increased risk of end-stage renal disease (ESRD) and cardiovascular morbidity and mortality
Experimental studies have demonstrated the involvement of an imbalance in angiogenesis-related factors in the progression of CKD [19,20,21,22,23,24,25] and the potential therapeutic effects on CKD achieved by modulating these factors [6,26,27,28,29,30,31,32,33]
An inverse correlation between the plasma levels of VASH-1 and age/blood pressure has been observed in CKD patients
Summary
Chronic kidney disease (CKD) is associated with an increased risk of end-stage renal disease (ESRD) and cardiovascular morbidity and mortality. Since the number of patients with ESRD is increasing worldwide, establishing biomarkers to predict renal functional deterioration and prevent the progression of CKD by initiating early medical intervention is required. Vasohibin-1 (VASH-1), an endogenous angiogenesis inhibitor, was originally identified in a microarray analysis assessing genes up-regulated by vascular endothelial growth factor (VEGF)-A, a major pro-angiogenic factor [7], in endothelial cells [8]. The critical role of VASH-1 in the maintenance of endothelial cells against cellular stressors and the regulatory mechanisms of its synthesis via posttranscriptional regulation mediated by the binding of HuR proteins to AU-rich elements in the 39 untranslated region of VASH-1 mRNAs have been reported [9]. The circulating and urinary levels of VASH-1 in patients with renal disorders have not been examined to date
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