Objective To investigate the expression change of sca-1 and c-kit in the calcified area of coronary atherosclerosis in rats, so as to provide clinical reference for further study of the mechanism of coronary atherosclerosis. Methods Thirty-two healthy adult SD rats were randomly divided into a normal control group (n=8) and an atherosclerotic calcification model group (n=24). The model was prepared by gavage of propylthiouracil, feeding with high fat and cholesterol diet and intraperitoneal injection of vitamin D3. After the model was successfully prepared, the expression changes of sca-1 and c-kit in the coronary artery tissues of the model group and the normal group were observed by immunohistochemistry and immunofluorescence techniques. Immunofluorescence technique was used to detect the co-expression of sca-1 and α-SMA. Western blotting was used to detect the differences of c-kit and sca-1 protein expression between model group and normal group. Results At the 12th week of modeling, the coronary artery wall of rats was significantly thickened, the intima was significant hyperplasia, the smooth muscle cells were arranged in a significant disorder, and there were necrotic substance deposition, lipid deposition and calcium nodule precipitation. Immunohistochemical and immunofluorescence results showed that sca-1+cells and c-kit+ cells were significantly higher in the intima, media and adventitia of coronary artery in atherosclerotic and calcified areas than those in the normal control group. Some cells have co-expression of sca-1 and α-SMA in the location of lesion. Western blotting result showed that the expressions of c-kit and sca-1 protein in atherosclerotic and calcified areas were higher than those in normal control group. Conclusions Sca-1+ cells and c-kit+ cells have the tendency to migrate to the calcification area of coronary atherosclerosis, and the mechanism needs to be further investigated.
Key words
Sca-1 /
/
/
C-kit /
/
/
Atherosclerotic calcification /
/
/
Immunohistochemistry /
/
/
Rat heart
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Jansen K, Steen AFD, Beusekom H, et al. Intravascular photoacoustic imaging of human coronary atherosclerosis[J].Optics Letters, 2011, 36(5):597-599.DOI: 10.1364/OL.36.000597.
[2] Feil S, Fehrenbacher B, Lukowski R, et al. Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis[J]. Circ Res. 2014;115(7):662-667. DOI: 10.1161/CIRCRESAHA.115.304634.
[3] Goldschmidt-Clermont PJ, Dong C, Seo DM, et al. Atherosclerosis, inflammation, genetics, and stem cells: 2012 update. Curr Atheroscler Rep. 2012;14(3):201-210. DOI:10.1007/s11883-012-0244-1.
[4] Tso C, Martinic G, Fan WH, et al. High-density lipoproteins enhance progenitor-mediated endothelium repair in mice[J]. Arterioscler Thromb Vasc Biol .2006,26(5):1144 –1149.DOI: 10.1161/01.ATV.0000216600.37436.cf.
[5] Hu Y , Zhang Z , Torsney E , et al. Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE- deficient mice[J]. J Clin Invest.2004,113(9):1258-1265.DOI: 10.1172/JCI19628.
[6] Kramann R , Goettsch C , Wongboonsin J , et al. Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease[J]. Cell Stem Cell. 2016,9(5):628–642.DOI: 10.1016/j.stem.2016.08.001.
[7] Wong MM, Winkler B, Karamariti E, et al. Sirolimus stimulates vascular stem/progenitor cell migration and differentiation into smooth muscle cells via epidermal growth factor receptor /extracellular signal-regulated kinase/β-catenin signaling pathway.[J]. Arterioscler Thromb Vasc Biol, 2013, 33(10):2397-2406.DOI: 10.1161/ATVBAHA. 113. 301595.
[8] Di MFCastaldo C, Nurzynska D, et al. Epithelial-mesenchymal transition of epicardial mesothelium is a source of cardiac CD117-positive stem cells in adult human heart.[J]. J Mol Cell Cardiol NLM.2010, 49(5):719-727.DOI: 10.1016/j.yjmcc.2010.05.013.
[9] Singla D, Wang J. Fibroblast growth factor-9 activates c-Kit progenitor cells and enhances angiogenesis in the infarcted diabetic heart[J]. Oxid Med Cell Longev.2016, 2016(5):1-12.DOI: 10.1155/2016/5810908.
[10]Nilsson J, Hansson GK, Shah PK. Immunomodulation of atherosclerosis: implications for vaccine development[J]. Arterioscler Thromb Vasc Biol, 2005, 25(1):18-28.DOI: 10.1161/01.ATV. 000014 9142.42590.a2.
[11]Lee JM, Jung J, Lee HJ, et al. Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells[J]. Int Immunopharmacol.2012, 13(2):219-224.DOI: 10.1016/j.intimp.2012.03.024.
[12]Pelliccia F, Cianfrocca C, Rosano G, et al. Role of endothelial progenitor cells in restenosis and progression of coronary atherosclerosis after percutaneous coronary intervention : a prospective study.[J]. Jacc. 2010, 3(1):87-89.DOI: 10.1016/j.jcin.2009.10.020.
[13]Zoll J, Fontaine V, Gourdy P, et al. Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition. Cardiovasc Res. 2008,77(3):471-480.DOI: 10.1093/cvr/cvm034.
[14]Cho HJ , Cho HJ , Kim HS, et al. Vascular progenitor cells with decalcifying potential: a step toward prevention or treatment of atherosclerotic vascular calcification[J]. Expert Rev Cardiovasc Ther. 2013, 11(8):937-939.DOI: 10.1586/14779072.2013.814875.
[15]van Berlo JH, Kanisicak O, Maillet M, et al. c-kit+ cells minimally contribute cardiomyocytes to the heart[J]. Nature. 2014 May 15;509(7500):337-341.DOI: 10.1038/nature13309.
[16]Zigmond ZM, Song L, Martinez L, et al. c-Kit expression in smooth muscle cells reduces atherosclerosis burden in hyperlipidemic mice[J]. Atherosclerosis. 2021, 324:133-140.DOI: 10.1016/j.atheroscle rosis.2021.03.004.
[17]Song L, Zigmond ZM, Martinez L, et al. c-Kit suppresses atherosclerosis in hyperlipidemic mice[J]. Am J Physiol Heart Circ Physiol, 2019, 317(4):H867-H876.DOI: 10.1152/ajpheart.00062.2019.
[18] Zhou P, Yu SN, Zhang HF, et al. c-kit+VEGFR-2+ Mesenchymal stem cells differentiate into cardiovascular cells and repair infarcted myocardium after transplantation [J], Stem Cell Rev Rep. 2022,19(1): 230-247. .DOI: 10.1007/s12015-022-10430-z.
PDF(5810 KB)
