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Endothelial Progenitor Cells in Patients with Acute Cerebrovascular Ischemia

Published online by Cambridge University Press:  23 September 2016

Askar Mohammad ,
Usman Ghani ,
Brenda Schwindt  and
Ashfaq Shuaib
Askar Mohammad
Affiliation:
Stroke Research Program, University of Alberta, Edmonton, Alberta, Canada
Usman Ghani
Affiliation:
Stroke Research Program, University of Alberta, Edmonton, Alberta, Canada
Brenda Schwindt
Affiliation:
Stroke Research Program, University of Alberta, Edmonton, Alberta, Canada
Ashfaq Shuaib*
Affiliation:
Stroke Research Program, University of Alberta, Edmonton, Alberta, Canada
*
Stroke Research Program, University of Alberta, Edmonton, Alberta, Canada
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Abstract

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Objective:

Statins have been shown to increase endothelial progenitor cells (EPCs) in patients with cardiovascular disease. However, there is no similar study that has been done on the patients recovering from cerebrovascular disease. We present the largest prospective study of statin therapy on EPC levels of patients recovering from stroke.

Method:

Our study subjects were treated with rosuvastatin (10 mg/day) over a period of 12 weeks. Blood was collected from these patients periodically and EPC levels were measured along with other biochemical parameters.

Results and Conclusions:

Our study shows that rosuvastatin treatment significantly reduces the low density lipoprotein (LDL) levels in the patients over the 12 weeks. However, we did not find any corresponding changes in the EPC levels during this time period. Earlier reports indicated that statin use could increase EPC proliferation. Our research, however, indicates that the in-vivo effects of rosuvastatin are not similar to those of previous reports. There may be several reasons for this lack of congruence between these two studies, including age of the study population, predominantly low high density lipoprotein (HDL) levels in our subjects and effects from other concomitant medications.

Résumé

RésuméObjectif:

Il a été démontré que les statines augmentent les cellules progénitrices endothéliales (CPE) chez les patients atteints de maladie cardiovasculaire. Cependant il n'existe pas d'étude similaire chez les patients en phase de récupération d'une maladie cérébrovasculaire. Nous présentons la plus grande étude prospective sur l'effet du traitement par les statines sur le niveau de CPE chez des patients en phase de récupération d'un accident vasculaire cérébral (AVC).

Méthodologie:

Les sujets ont reçu de la rosuvastatine (10 mg par jour) pendant 12 semaines et des prises de sang ont été faites périodiquement. Les niveaux de CPE ainsi que d'autres paramètres biochimiques ont été mesurés.

Résultats et conclusions:

Notre étude démontre que le traitement par la rosuvastatine a diminué significativement le niveau de LDL chez les patients au cours des 12 semaines de traitement. Cependant, nous n'avons pas observé de changement dans le niveau de CPE pendant cette période. Des études antérieures indiquaient que les statines pouvaient augmenter la prolifération des CPE. Cependant, notre étude indique que les effets de la rosuvastatine in vivo ne sont pas similaires à ceux observés dans une étude antérieure. Plusieurs raisons peuvent être invoquées pour expliquer cette divergence entre ces deux études, dont l'âge des sujets étudiés, un taux de HDL généralement bas chez nos sujets et les effets des médicaments concomitants.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 37 , Issue 6 , November 2010 , pp. 797 - 802
Copyright
Copyright © The Canadian Journal of Neurological 2010

References

1. Straus, SE, Majumdar, SR, McAlister, FA. New evidence for stroke prevention: scientific review. JAMA. 2002;288:1388–95.10.1001/jama.288.11.138812234233Google Scholar
2. Choy, JC, Granville, DJ, Hunt, DW, McManus, BM. Endothelial cell apoptosis: biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol. 2001;33:1673–90.10.1006/jmcc.2001.141911549346Google Scholar
3. Bisoendial, RJ, Hovingh, GK, de, GE, Kastelein, JJ, Lansberg, PJ, Stroes, ES. Measurement of subclinical atherosclerosis: beyond risk factor assessment. Curr Opin Lipidol. 2002;13:595–603.10.1097/00041433-200212000-0000212441883Google Scholar
4. Bisoendial, RJ, Hovingh, GK, Levels, JH, et al. Restoration of endothelial function by increasing high-density lipoprotein in subjects with isolated low high-density lipoprotein. Circulation. 2003;107:2944–8.10.1161/01.CIR.0000070934.69310.1A12771001Google Scholar
5. Blake, GJ, Ridker, PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001;89:763–71.10.1161/hh2101.09927011679405Google Scholar
6. Asahara, T, Isner, JM. Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res. 2002;11:171–8.10.1089/15258160275365838511983091Google Scholar
7. Doyle, B, Metharom, P, Caplice, NM. Endothelial progenitor cells. Endothelium. 2006;13:403–10.10.1080/1062332060106165617169772Google Scholar
8. Dimmeler, S, Aicher, A, Vasa, M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001;108:391–-7.10.1172/JCI20011315211489932Google Scholar
9. Kureishi, Y, Luo, Z, Shiojima, I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6:1004–10.10.1038/7951010973320Google Scholar
10. Vasa, M, Fichtlscherer, S, Adler, K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation. 2001;103:2885–90.10.1161/hc2401.09281611413075Google Scholar
11. Ghani, U, Shuaib, A, Salam, A, et al. Endothelial progenitor cells during cerebrovascular disease. Stroke. 2005;36:151–3.10.1161/01.STR.0000149944.15406.1615576657Google Scholar
12. Amarenco, P, Bogousslavsky, J, Callahan, A III, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–59.10.1056/NEJMoa06189416899775Google Scholar
13. Amarenco, P, Goldstein, LB, Szarek, M, et al. 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. Stroke. 2007;38:3198–204.10.1161/STROKEAHA.107.49310617962589Google Scholar
14. Hill, JM, Zalos, G, Halcox, JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.10.1056/NEJMoa02228712584367Google Scholar
15. Adams, V, Lenk, K, Linke, A, et al. Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia. Arterioscler Thromb Vasc Biol. 2004;24:684–90.10.1161/01.ATV.0000124104.23702.a014988094Google Scholar
16. Landmesser, U, Hornig, B, Drexler, H. Endothelial function: a critical determinant in atherosclerosis? Circulation. 2004;109:II27–II33.AMBIGUOUS (703 citations)Google Scholar
17. Ito, H, Rovira, II, Bloom, ML, et al. Endothelial progenitor cells as putative targets for angiostatin. Cancer Res. 1999;59:5875–7.10606226Google Scholar
18. Masuda, H, Kalka, C, Asahara, T. Endothelial progenitor cells for regeneration. Hum Cell. 2000;13:153–60.11329932Google Scholar
19. Walter, DH, Dimmeler, S. Endothelial progenitor cells: regulation and contribution to adult neovascularization. Herz. 2002;27:579–88.10.1007/s00059-002-2427-y12439630Google Scholar
20. Asahara, T. Endothelial progenitor cells for neovascularization. Ernst Schering Res Found Workshop. 2003;211–16.Google Scholar
21. Rumpold, H, Wolf, D, Koeck, R, Gunsilius, E. Endothelial progenitor cells: a source for therapeutic vasculogenesis? J Cell Mol Med. 2004;8:509–18.10.1111/j.1582-4934.2004.tb00475.x15601579Google Scholar
22. Hill, JM, Finkel, T, Quyyumi, AA. Endothelial progenitor cells and endothelial dysfunction. Vox Sang. 2004;87 Suppl 2:31–7.10.1111/j.1741-6892.2004.00451.x15209875Google Scholar
23. Yoder, MC, Mead, LE, Prater, D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/ progenitor cell principals. Blood. 2007;109:1801–9.10.1182/blood-2006-08-04347117053059Google Scholar
24. Noor, R, Shuaib, U, Wang, CX, et al. High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis. Atherosclerosis. 2007;192:92–9.10.1016/j.atherosclerosis.2006.06.02316884727Google Scholar
25. Hoffmann, J, Haendeler, J, Aicher, A, et al. Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide. Circ Res. 2001;89:709–15.10.1161/hh2001.09779611597994Google Scholar
26. Sirker, AA, Astroulakis, ZM, Hill, JM. Vascular progenitor cells and translational research: the role of endothelial and smooth muscle progenitor cells in endogenous arterial remodelling in the adult. Clin Sci (Lond). 2009;116:283–99.10.1042/CS2008000119138170Google Scholar
27. Ridker, PM, Danielson, E, Fonseca, FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175–82.10.1016/S0140-6736(09)60447-519329177Google Scholar
28. Hristov, M, Fach, C, Becker, C, et al. Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment. Atherosclerosis. 2007;192:413–20.10.1016/j.atherosclerosis.2006.05.03116837000Google Scholar