Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria

Po Hsun Huang, Shao Sung Huang, Yung Hsiang Chen, Chih Pei Lin, Kuang-Hsing Chiang, Jia Shiong Chen, Hsiao Ya Tsai, Feng Yen Lin, Jaw Wen Chen, Shing Jong Lin

研究成果: 雜誌貢獻文章同行評審

81 引文 斯高帕斯(Scopus)

摘要

Objective: Microalbuminuria is associated with an increased risk for all-cause and cardiovascular mortality, but the pathophysiologic mechanism underlying the association between urinary albumin excretion and cardiovascular disease remains unclear. Here, we tested the hypothesis that enhanced endothelial apoptotic microparticles and decreased endothelial progenitor cell (EPC) levels might contribute to the pathophysiology of microalbuminuria or macroalbuminuria in cardiovascular disease. Methods: Flow cytometry was used to assess endothelial cell apoptosis and circulating EPC levels by quantification of circulating CD31+/annexin V+ apoptotic microparticles and EPC markers (defined as KDRCD133, CD34CD133, CD34KDR) in peripheral blood. Results: In total, 125 patients with hypertension were enrolled in the study, of whom 80 patients (64%) were with normoalbuminuria (albumin excretion rate of <20 μg/min, overnight urine samples), 35 patients (28%) with microalbuminuria (an albumin excretion rate of 20-200 μg/min), and 10 patients (8%) with macroalbuminuria (an albumin excretion rate >200 μg/min). Compared to hypertensive patients with normoalbuminuria, patients with microalbuminuria or macroalbuminuria had significantly more diabetes (P = 0.005), higher systolic blood pressure (P = 0.018), and elevated serum creatinine levels (P < 0.001). Among the three groups, patients with microalbuminuria or macroalbuminuria had significantly increased CD31/annexin V apoptotic microparticles (1.8 ± 2.2 versus 3.0 ± 4.3 versus 5.2 ± 6.2%, P = 0.044) and decreased circulating EPC numbers (P < 0.05). By multivariate analysis, CD31/annexin V apoptotic microparticle level was an independent predictor of urinary albumin excretion rate in hypertensive patients (P < 0.001). Microparticles isolated from hypertensive patients with microalbuminuria or macroalbuminuria attenuated EPC proliferation, migration, and increased H2O2 production, cellular senescence and apoptosis in comparison with those from hypertensive patients with normoalbuminuria. Conclusion: These findings suggest that hypertensive patients with microalbuminuria or macroalbuminuria have increased endothelial apoptotic microparticles and decreased circulating EPC levels, which may contribute to atherosclerotic disease progression and enhanced cardiovascular risk in hypertensive patients with nephropathy.

原文英語
頁(從 - 到)1655-1665
頁數11
期刊Journal of Hypertension
28
發行號8
DOIs
出版狀態已發佈 - 8月 2010

ASJC Scopus subject areas

  • 內科學
  • 生理學
  • 心臟病學與心血管醫學

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