Increased levels of circulating endothelial progenitor cells in patients with ischaemic stroke treated with statins during acute phase

被引:73
作者
Sobrino, T. [1 ]
Blanco, M. [1 ]
Perez-Mato, M. [1 ]
Rodriguez-Yanez, M. [1 ]
Castillo, J. [1 ]
机构
[1] Univ Santiago de Compostela, Clin Neurosci Res Lab, Dept Neurol, Hosp Clin Univ,IDIS, Santiago De Compostela 15706, Spain
关键词
endothelial progenitor cells; ischaemic stroke; nitric oxide; outcome; statins; NITRIC-OXIDE; GROWTH-FACTOR; CEREBROVASCULAR-DISEASE; ANGIOGENESIS; ATORVASTATIN; RECRUITMENT; WITHDRAWAL; PATHWAY; ATTACK; BRAIN;
D O I
10.1111/j.1468-1331.2012.03770.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Background and purpose Endothelial progenitor cells (EPCs) have been suggested to be a therapeutic option in ischaemic stroke. Our aim was to study whether statin treatment during acute phase could increase circulating EPCs after acute ischaemic stroke. Methods We studied 48 patients with a first-ever non-lacunar ischaemic stroke (<12 h from stroke onset). Sixteen patients received statin treatment (20 mg atorvastatin/day) during the first 4 days. We defined the EPC increment during the first week as the difference in the number of early outgrowth colony-forming unit-endothelial cell (CFU-EC) between day 7 and at admission (previous to atorvastatin treatment). Serum levels of vascular endothelial growth factor and active matrix metalloproteinase 9 (determined by ELISA), and nitric oxide metabolites (NOx) (determined by high-performance liquid chromatography) were measured at admission, 24 and 72 h, and day 7. Results Colony-forming unit-endothelial cells were similar at baseline between patients treated (n = 16) and non-treated (n = 32) with statins (10.1 +/- 3.9 vs. 7.9 +/- 6.9 CFU-EC, P = 0.223). However, patients treated with statins showed a higher EPC increment (24.0 +/- 17.3 vs. 6.0 +/- 17.8 CFU-EC, P = 0.002) during the first week. An EPC increment >= 4 CFU-EC predicted with the highest sensitivity (88%) and specificity (92%) the probability of good outcome (area under the curve 0.903, P < 0.0001). Statin treatment (OR, 13.1; CI 95%, 2.276.9, P = 0.004) was independently associated with an EPC increment >= 4 CFU-EC after adjustment for confounder factors, but this association was lost when adjusting for NOx levels. Conclusions Statin treatment for 4 days may increase circulating EPC levels, probably by NO-related mechanisms.
引用
收藏
页码:1539 / 1546
页数:8
相关论文
共 32 条
[1]
CLASSIFICATION OF SUBTYPE OF ACUTE ISCHEMIC STROKE - DEFINITIONS FOR USE IN A MULTICENTER CLINICAL-TRIAL [J].
ADAMS, HP ;
BENDIXEN, BH ;
KAPPELLE, LJ ;
BILLER, J ;
LOVE, BB ;
GORDON, DL ;
MARSH, EE ;
KASE, CS ;
WOLF, PA ;
BABIKIAN, VL ;
LICATAGEHR, EE ;
ALLEN, N ;
BRASS, LM ;
FAYAD, PB ;
PAVALKIS, FJ ;
WEINBERGER, JM ;
TUHRIM, S ;
RUDOLPH, SH ;
HOROWITZ, DR ;
BITTON, A ;
MOHR, JP ;
SACCO, RL ;
CLAVIJO, M ;
ROSENBAUM, DM ;
SPARR, SA ;
KATZ, P ;
KLONOWSKI, E ;
CULEBRAS, A ;
CAREY, G ;
MARTIR, NI ;
FICARRA, C ;
HOGAN, EL ;
CARTER, T ;
GURECKI, P ;
MUNTZ, BK ;
RAMIREZLASSEPAS, M ;
TULLOCH, JW ;
QUINONES, MR ;
MENDEZ, M ;
ZHANG, SM ;
ALA, T ;
JOHNSTON, KC ;
ANDERSON, DC ;
TARREL, RM ;
NANCE, MA ;
BUDLIE, SR ;
DIERICH, M ;
HELGASON, CM ;
HIER, DB ;
SHAPIRO, RA .
STROKE, 1993, 24 (01) :35-41
[2]
Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack - The stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial [J].
Amarenco, Pierre ;
Goldstein, Larry B. ;
Szarek, Michael ;
Sillesen, Henrik ;
Rudolph, Amy E. ;
Callahan, Alfred, III ;
Hennerici, Michael ;
Simunovic, Lisa ;
Zivin, Justin A. ;
Welch, K. Michael A. .
STROKE, 2007, 38 (12) :3198-3204
[3]
Amarenco P, 2006, NEW ENGL J MED, V355, P549
[4]
VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells [J].
Asahara, T ;
Takahashi, T ;
Masuda, H ;
Kalka, C ;
Chen, DH ;
Iwaguro, H ;
Inai, Y ;
Silver, M ;
Isner, JM .
EMBO JOURNAL, 1999, 18 (14) :3964-3972
[5]
Statin treatment withdrawal in ischemic stroke -: A controlled randomized study [J].
Blanco, M. ;
Nombela, F. ;
Castellanos, M. ;
Rodriguez-Yanez, M. ;
Garcia-Gil, M. ;
Leira, R. ;
Lizasoain, I. ;
Serena, J. ;
Vivancos, J. ;
Moro, M. A. ;
Davalos, A. ;
Castillo, J. .
NEUROLOGY, 2007, 69 (09) :904-910
[6]
REORGANIZATION OF THE CEREBRAL VASCULATURE FOLLOWING ISCHAEMIA [J].
Brea, D. ;
Sobrino, T. ;
Ramos-Cabrer, P. ;
Castillo, J. .
REVISTA DE NEUROLOGIA, 2009, 49 (12) :645-654
[7]
Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice [J].
Chen, JL ;
Zhang, CL ;
Jiang, H ;
Li, Y ;
Zhang, LJ ;
Robin, A ;
Katakowski, M ;
Lu, M ;
Chopp, M .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2005, 25 (02) :281-290
[8]
Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke [J].
Chen, JL ;
Zhang, ZG ;
Li, Y ;
Wang, Y ;
Wang, L ;
Jiang, H ;
Zhang, CL ;
Lu, M ;
Katakowski, M ;
Feldkamp, CS ;
Chopp, M .
ANNALS OF NEUROLOGY, 2003, 53 (06) :743-751
[9]
Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke [J].
Chu, Kon ;
Jung, Keun-Hwa ;
Lee, Soon-Tae ;
Park, Hee-Kwon ;
Sinn, Dong-In ;
Kim, Jeong-Min ;
Kim, Dong-Hyun ;
Kim, Jin-Hee ;
Kim, Se-Jeong ;
Song, Eun-Cheol ;
Kim, Manho ;
Lee, Sang Kun ;
Roh, Jae-Kyu .
STROKE, 2008, 39 (05) :1441-1447
[10]
*COM AD HOC GRUP E, 2004, GUIA DIAGN TRAT ICT