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

Research output: Contribution to journalArticle

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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 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 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.

Original languageEnglish
Pages (from-to)1655-1665
Number of pages11
JournalJournal of Hypertension
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Annexin A5
Albumins
Cardiovascular Diseases
Endothelial Progenitor Cells
Apoptosis
Hypertension
Cell Aging
Cell Movement
Disease Progression
Creatinine
Flow Cytometry
Multivariate Analysis
Endothelial Cells
Cell Count
Cell Proliferation
Blood Pressure
Mortality

Keywords

  • CD31/Annexin V apoptotic microparticles
  • endothelial progenitor cell
  • hypertension
  • microalbuminuria

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria. / Huang, Po Hsun; Huang, Shao Sung; Chen, Yung Hsiang; Lin, Chih Pei; Chiang, Kuang Hsing; Chen, Jia Shiong; Tsai, Hsiao Ya; Lin, Feng Yen; Chen, Jaw Wen; Lin, Shing Jong.

In: Journal of Hypertension, Vol. 28, No. 8, 08.2010, p. 1655-1665.

Research output: Contribution to journalArticle

Huang, Po Hsun ; Huang, Shao Sung ; Chen, Yung Hsiang ; Lin, Chih Pei ; Chiang, Kuang Hsing ; Chen, Jia Shiong ; Tsai, Hsiao Ya ; Lin, Feng Yen ; Chen, Jaw Wen ; Lin, Shing Jong. / Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria. In: Journal of Hypertension. 2010 ; Vol. 28, No. 8. pp. 1655-1665.
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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 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 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.",
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T1 - Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria

AU - Huang, Po Hsun

AU - Huang, Shao Sung

AU - Chen, Yung Hsiang

AU - Lin, Chih Pei

AU - Chiang, Kuang Hsing

AU - Chen, Jia Shiong

AU - Tsai, Hsiao Ya

AU - Lin, Feng Yen

AU - Chen, Jaw Wen

AU - Lin, Shing Jong

PY - 2010/8

Y1 - 2010/8

N2 - 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 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.

AB - 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 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.

KW - CD31/Annexin V apoptotic microparticles

KW - endothelial progenitor cell

KW - hypertension

KW - microalbuminuria

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