Increased circulating CD31+/annexin V+ apoptotic... : Journal of Hypertension (original) (raw)

Original papers: Endothelium

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

Huang, Po-Hsuna,d,e,*; Huang, Shao-Sunga,e,*; Chen, Yung-Hsiangg; Lin, Chih-Peic,f; Chiang, Kuang-Hsinga,e; Chen, Jia-Shiongf; Tsai, Hsiao-Yad; Lin, Feng-Yeni; Chen, Jaw-Wena,b,e,h; Lin, Shing-Jonga,b,d,e

aDivision of Cardiology, Department of Internal Medicine, Taiwan

bDepartment of Medical Research and Education, Taiwan

cDivision of General Laboratory, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taiwan

dInstitute of Clinical Medicine, Taiwan

eCardiovascular Research Center, Taiwan

fDepartment of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan

gGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

hInstitute and Department of Pharmacology, National Yang-Ming University, Taiwan

iDivision of Anesthesiology, Taipei Medical University Hospital and Department of Anesthesiology, School of Medicine, Taipei Medical University, Taipei, Taiwan.

*P.-O.H. and S.-S.H. contributed equally to this work.

Received 7 June, 2009

Revised 28 February, 2010

Accepted 25 March, 2010

Correspondence to Professor Shing-Jong Lin, Department of Medical Research and Education, Taipei Veterans General Hospital, No.201, Sec.2, Shih-Pai Road, Taipei, Taiwan Tel: +886 2 2875 7434; fax: +886 2 2876 3336; e-mail: [email protected]

Abstract

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 KDR+CD133+, CD34+CD133+, CD34+KDR+) 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.