Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension.
OBJECTIVE
Recent studies have revealed an association between coronary risk factors and both the number and function of bone marrow-derived endothelial progenitor cells (EPCs). Although hypertension is an important coronary risk factor, the influence to the EPCs is not fully understood. We investigated the effect of hypertension on EPC senescence.


METHODS
Experimental study We investigated the number and senescence of EPCs in spontaneously hypertensive rats (SHR/Izm) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. EPCs were isolated from peripheral blood of rats and were characterized. EPC senescence was detected by acidic beta-galactosidase staining. In addition, we measured the telomerase activity using polymerase chain reaction-enzyme-linked immunosorbent assay.


METHODS
EPCs were isolated from peripheral blood samples in 37 patients with essential hypertension. After ex-vivo cultivation, we detected senescence and measured the telomerase activity. The total severity index of hypertension-induced organ damage was calculated by the summation of each severity index in the classification of hypertension severity by Tokyo University (1984).


RESULTS
Experimental study The EPC senescence in SHR/Izm and DOCA-salt hypertensive rats was significantly increased compared with that of control rats. The telomerase activities in SHR/Izm and DOCA-salt hypertensive sensitive rats were also significantly lowered compared with those of control rats. Clinical study Compared with the control group, EPCs from hypertensive patients showed accelerated senescence and also showed reduced telomerase activity. In hypertensive patients, the degree of hypertension-induced organ damage was negatively correlated with telomerase activity, and was positively correlated with EPC senescence.


CONCLUSIONS
EPC senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension, which may be related to telomerase inactivation. The hypertension-induced EPC senescence may affect the process of vascular remodeling.
Imanishi
Toshio
T
Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan. t-imani@wakayama-med.ac.jp
Moriwaki
Chizu
C
Hano
Takuzo
T
Nishio
Ichiro
I
D000368:Aged; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D003900:Desoxycorticosterone / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013234:Stem Cells / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D003900:Desoxycorticosterone; D019098:Telomerase; D001616:beta-Galactosidase