Rupture of the coronary artery fibrous cap is a common cause of myocardial infarction, and bone marrow derived cells could play a role in preventing plaque rupture. It is currently unknown whether smooth muscle cells within coronary artery fibrous cap formation are of mature phenotype. Objective. To characterize cells expressing bone marrow stem cells of embryonic type (ESC) markers in coronary artery fibrous cap formation. Design. New Zealand White rabbits were fed a diet supplemented with 0.5% cholesterol？？+？？1% methionine？？+？？5% peanut oil for 4 weeks and then a normal diet for 9 weeks. The left main coronary artery was excised from the heart, processed for paraffin and immunohistochemistry was performed by standard techniques. Results. Oct-4, SSEA 1, 3, and 4 were all present within in atherosclerotic plaque core, codistributed with RAM-11, and were sparingly found in the fibrous cap, but TRA-1-60 and TRA-1-81 positive cells were scarce. Core but not fibrous cap smooth muscle (SMC actin+) cells also showed codistribution with ESC markers. Conclusions. These results suggest that smooth muscle cells present in the fibrous cap do not express ESC markers, indicative of a mature cell. 1. Introduction Rupture of coronary artery fibrous cap is a major cause of myocardial infarct [1]. Inhibition of the HMG CoA reductase enzyme and renin angiotensin system have been one of the most successful therapies in reducing this burden, possibly by increasing the formation of a stable fibrous cap. Interestingly, stem cells can be regulated by the same pharmacological therapy, providing a possible explanation as to the beneficial effects of treatments [2]. For example, simvastatin has been shown to normalise endothelial progenitor cells in obese patients to those observed in nonobese controls [3] and angiotensin II receptor blockers increased endothelial progenitor cells in diabetic patients [4], and modulation of these types of cells is also observed with angiotensin converting enzyme inhibitors [5]. Thus, the characterization of stem cell populations in coronary artery disease will aid in understanding whether standard pharmacological treatments can affect the population of such undifferentiated cells. Recent studies have suggested that the origin of smooth muscle cells in atherosclerotic fibrous caps might not be from the circulation [6] as had been enthusiastically embraced but derive from the local medial SMC layer [7, 8]. Thus, in this study, it was hypothesised that if smooth muscle cells originated from the circulation and were of primitive type, then the cells
References
[1]
R. Corti, M. E. Farkouh, and J. J. Badimon, “The vulnerable plaque and acute coronary syndromes,” American Journal of Medicine, vol. 113, no. 8, pp. 668–680, 2002.
[2]
T. Umemura and Y. Higashi, “Endothelial progenitor cells: therapeutic target for cardiovascular diseases,” Journal of Pharmacological Sciences, vol. 108, no. 1, pp. 1–6, 2008.
[3]
P. E. Westerweel, F. L. J. Visseren, G. R. Hajer et al., “Endothelial progenitor cell levels in obese men with the metabolic syndrome and the effect of simvastatin monotherapy vs. simvastatin/ezetimibe combination therapy,” European Heart Journal, vol. 29, no. 22, pp. 2808–2817, 2008.
[4]
F. H. Bahlmann, K. de Groot, O. Mueller, B. Hertel, H. Haller, and D. Fliser, “Stimulation of endothelial progenitor cells: a new putative therapeutic effect of angiotensin II receptor antagonists,” Hypertension, vol. 45, no. 4, pp. 526–529, 2005.
[5]
C.-H. Wang, S. Verma, I.-C. Hsieh et al., “Enalapril increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system,” Journal of Molecular and Cellular Cardiology, vol. 41, no. 1, pp. 34–43, 2006.
[6]
M. Sata, A. Saiura, A. Kunisato et al., “Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis,” Nature Medicine, vol. 8, no. 4, pp. 403–409, 2002.
[7]
J. F. Bentzon, C. S. Sondergaard, M. Kassem, and E. Falk, “Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice,” Circulation, vol. 116, no. 18, pp. 2053–2061, 2007.
[8]
J. F. Bentzon, C. Weile, C. S. Sondergaard, J. Hindkjaer, M. Kassem, and E. Falk, “Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in apoE knockout mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 12, pp. 2696–2702, 2006.
[9]
W. Wojakowski, M. Kucia, R. Liu et al., “Circulating very small embryonic-like stem cells in cardiovascular disease,” Journal of Cardiovascular Translational Research, vol. 4, no. 2, pp. 138–144, 2011.
[10]
W. Wojakowski, M. Kucia, E. Zuba-Surma et al., “Very small embryonic-like stem cells in cardiovascular repair,” Pharmacology and Therapeutics, vol. 129, no. 1, pp. 21–28, 2011.
[11]
S. Berger and L. Lavie, “Endothelial progenitor cells in cardiovascular disease and hypoxia—potential implications to obstructive sleep apnea,” Translational Research, vol. 158, no. 1, pp. 1–13, 2011.
[12]
Y.-C. Huang, Z.-M. Yang, X.-H. Chen et al., “Isolation of mesenchymal stem cells from human placental decidua basalis and resistance to hypoxia and serum deprivation,” Stem Cell Reviews and Reports, vol. 5, no. 3, pp. 247–255, 2009.
[13]
A. Zulli, B. F. Buxton, M. J. Black, and D. L. Hare, “CD34 Class III positive cells are present in atherosclerotic plaques of the rabbit model of atherosclerosis,” Histochemistry and Cell Biology, vol. 124, no. 6, pp. 517–522, 2005.
[14]
A. Zulli, B. F. Buxton, M. J. Black, and D. L. Hare, “Embryonic stem cells markers are present within rabbit atherosclerotic plaques,” Histology and Histopathology, vol. 23, no. 6, pp. 741–746, 2008.
[15]
A. Zulli, B. F. Buxton, M. Merrilees, and D. L. Hare, “Human diseased arteries contain cells expressing leukocytic and embryonic stem cell markers,” Human Pathology, vol. 39, no. 5, pp. 657–665, 2008.
[16]
M. Pesce and H. R. Sch？ler, “Oct-4: gatekeeper in the beginnings of mammalian development,” Stem Cells, vol. 19, no. 4, pp. 271–278, 2001.
[17]
M. Yanagisawa and R. K. Yu, “The expression and functions of glycoconjugates in neural stem cells,” Glycobiology, vol. 17, no. 7, pp. 57R–74R, 2007.
[18]
E. Gilboa, “The makings of a tumor rejection antigen,” Immunity, vol. 11, no. 3, pp. 263–270, 1999.
[19]
A. Zulli and D. L. Hare, “High dietary methionine plus cholesterol stimulates early atherosclerosis and late fibrous cap development which is associated with a decrease in GRP78 positive plaque cells,” International Journal of Experimental Pathology, vol. 90, no. 3, pp. 311–320, 2009.
[20]
A. Zulli, S. Rai, B. F. Buxton, L. M. Burrell, and D. L. Hare, “Co-localization of angiotensin-converting enzyme 2-, octomer-4- and CD34-positive cells in rabbit atherosclerotic plaques,” Experimental Physiology, vol. 93, no. 5, pp. 564–569, 2008.
[21]
C. Urbich and S. Dimmeler, “Endothelial progenitor cells: characterization and role in vascular biology,” Circulation Research, vol. 95, no. 4, pp. 343–353, 2004.
[22]
J.-S. Silvestre, A. Gojova, V. Brun et al., “Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition,” Circulation, vol. 108, no. 23, pp. 2839–2842, 2003.
[23]
J. George, A. Afek, A. Abashidze et al., “Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 12, pp. 2636–2641, 2005.
[24]
P. Libby, “Inflammation in atherosclerosis,” Nature, vol. 420, no. 6917, pp. 868–874, 2002.
[25]
S. Bonde, M. Pedram, R. Stultz, and N. Zavazava, “Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells,” FASEB Journal, vol. 24, no. 2, pp. 364–373, 2010.
[26]
M. Wang, J. Zhang, L.-Q. Jiang et al., “Proinflammatory profile within the grossly normal aged human aortic wall,” Hypertension, vol. 50, no. 1, pp. 219–227, 2007.
[27]
J. H. Campbell and G. R. Campbell, “The cell biology of atherosclerosis—new developments,” Australian and New Zealand Journal of Medicine, vol. 27, no. 4, pp. 497–500, 1997.
[28]
R. J. Dilley, J. K. McGeachie, and F. J. Prendergast, “A review of the proliferative behaviour, morphology and phenotypes of vascular smooth muscle,” Atherosclerosis, vol. 63, no. 2-3, pp. 99–107, 1987.
[29]
K. Noaksson, N. Zoric, X. Zeng et al., “Monitoring differentiation of human embryonic stem cells using real-time PCR,” Stem Cells, vol. 23, no. 10, pp. 1460–1467, 2005.
[30]
J. R. Tejedo, R. Tapia-Limonchi, S. Mora-Castilla et al., “Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival,” Cell Death and Disease, vol. 1, no. 10, article e80, 2010.
