Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria.
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 microg/min, overnight urine samples), 35 patients (28%) with microalbuminuria (an albumin excretion rate of 20-200 microg/min), and 10 patients (8%) with macroalbuminuria (an albumin excretion rate >200 microg/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.


CONCLUSIONS
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.
Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
Po-Hsun
PH
Huang
Shao-Sung
SS
Huang
Yung-Hsiang
YH
Chen
Chih-Pei
CP
Lin
Kuang-Hsing
KH
Chiang
Jia-Shiong
JS
Chen
Hsiao-Ya
HY
Tsai
Feng-Yen
FY
Lin
Jaw-Wen
JW
Chen
Shing-Jong
SJ
Lin
D000419:Albuminuria / Q000097:blood / Q000150:complications / Q000473:pathology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000473:pathology*; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
D017304:Annexin A5; D019408:Platelet Endothelial Cell Adhesion Molecule-1