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Cardiomyocyte spontaneous regeneration following isoproterenol-induced left ventricular injury in rats
CAI Xin-hua* CAI Qing-hui ZHANG Yong-chun TIAN Xiang-qin
Acta Anatomica Sinica ›› 2015, Vol. 46 ›› Issue (6) : 824-831.
Cardiomyocyte spontaneous regeneration following isoproterenol-induced left ventricular injury in rats
Objective The notion of the adult heart as a terminally differentiated organ without the potential for self-renewal has been undermined by the identification of a subpopulation of proliferating cardiomyocytes in both the healthy and pathological states. Our purpose is to determine whether the expression of stem cell markers was associated with the spontaneous regeneration of cardiomyocytes in rats following isoproterenol hydrochloride (ISO)-induced cardiac necrosis.
Methods Rats (n=40) were injected subcutaneously with 4 mg/(kg.d) ISO for 7 days. The morphological structures were observed, the expression of stem cell and caridomyocyte markers were detected, and the characteristics of proliferation cell were surveyed in the necrotic area utilizing morphology, immunofluorescene and EdU labeling technology. Results The histopathological examination showed that the ischemic necrosis was limited to the area of the myocardium near the endocardium. A small number of round or ellipsoid and rod-shaped cells with strongly stained acidophilic cytoplasm were dispersed throughout the necrotic LV tissue. The ultrastructure analyses showed that the rod-shaped cells had the features similar to those of naive cardiomyocytes. The immunofluorescent staining showed that c-kit+/gata+ cells, nanog+ cells, CD34+/gata+ cells and CD34+/factor Ⅷ+ cells were present in the necrotic tissue. The EdU labeling showed that the cTnI+ cells in the necrotic area were actively proliferating cardiomyocytes. Conclusion Cardiac stem cells expressing c-kit, nanog, or CD34 participate in the spontaneous regeneration of necrotic area caused by ISO. The naive cardiomyocytes are formed in necrotic area. The CD34+ stem cells participate in the repair of the micro-vessel in the necrotic area of the myocardium.
Cardiac regeneration / Stem cell marker / Cardiomyocyte marker / Isoproterenol hydrochloride / EdU labeling / Immunofluorescence / Rat
［1］Anversa P, Kajstura J, Leri A, et al. Life and death of cardiac stem cells: a paradigm shift in cardiac biology［J］. Circulation, 2006,113(11):1451-1463.
［2］Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocytes divide after myocardial infarction［J］. N Engl J Med, 2001,344(23):1750-1757.
［3］Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration［J］. Cell, 2003,114(6):763-776.
［4］Tang XL, Rokosh G, Sanganalmath SK, et al. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction［J］. Circulation, 2010, 121(2):293-305.
［5］Rota M, Padin-Iruegas ME, Misao Y, et al. Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function［J］. Circ Res, 2008, 103(1): 107-116.
［6］Faulx MD, Ernsberger P, Vatner D, et al. Strain-dependent-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice［J］. Am J Physiol Heart Circ Physiol, 2005, 289(1): H30-H36.
［7］Boluyt MO, Long X, Eschenhagen T, et al. Isoproterenol infusion induces alterations in expression of hypertrophy-associated genes in rat heart［J］. Am J Physi, 1995, 269(2Pt2): H638-647.
［8］Brooks WW, Conrad CH. Isoproterenol-induced myocardial injury and diastolic dysfunction in mice: structural and functional correlates［J］. Comp Med, 2009, 59(4): 339-343.［9］Marques FD, Ferreira AJ, Sinisterra RD, et al. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats［J］. Hypertension, 2011, 57(3):477-483.
［10］Teerlink JR, Pfeffer JM, Pfeffer MA. Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats［J］. Circ Res, 1994, 75(1):105-113.
［11］Benjamin IJ, Jalil JE, Tan LB, et al. Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis［J］. Circ Res, 1989, 65(3):657-670.
［12］Bearzi C, Rota M, Hosoda T, et al. Human cardiac stem cells［J］. Proc Natl Acad Sci USA, 2007, 104(35):14068-14073.
［13］Rupp S, Bauer J, von Gerlach S, et al. Pressure overload leads to an increase of cardiac resident stem cells［J］. Basic Res Cardiol, 2012, 107(2): 252.
［14］Li N, Pasha Z, Ashraf M. Reversal of ischemic cardiomyopathy with Sca-1+ stem cells modified with multiple growth factors［J］. PLoS One, 2014, 9(4):e93645.
［15］Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and muring heart［J］. Circ Res, 2004, 95(9):911-921.
［16］Martin CM, Meeson AP, Robertson SM, et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identified cardiac SP cells in the developing and adult heart［J］. Dev Biol, 2004, 265(1):262-275.
［17］Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation and fusion after infarction［J］. Proc Nati Acad Sci, 2003, 100(21):12313-12318.
［18］Riekstina U, Cakstina I, Parfejevs V, et al. Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis［J］. Stem Cell Rev, 2009, 5(4): 378-386.
［19］Zhang S, Ma X, Yao K, et al. Combination of CD34-positive cell subsets with infarcted myocardium-like matrix stiffness: a potential solution to cell-based cardiac repair［J］. J Cell Mol Med, 2014,18(6):1236-1238.
［20］Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein nanog is required for maintenance of pluripotency in mouse epiblast and ES cells［J］. Cell, 2003, 113(5):631-642.
［21］Li TS, Cheng K, Lee ST, et al. Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair［J］. Stem Cells, 2010, 28(11): 2088-2098.
［22］Bellafiore M, Sivverini G, Cappello F, et al. Research of cardiomyocyte precursors in adult rat heart［J］. Tissue Cell, 2006, 38(6):345-351.
［23］Abdel-Latif A, Zuba-Surma EK, Ziada KM, et al. Evidence of mobilization of pluripotent stem cells into peripheral blood of patients with myocardial ischemia［J］. Exp Hematol, 2010, 38(12):1131-1142.
［24］Wojakowski W, Kucia M, Liu R, et al. Circulating very small embryonic-like stem cells in cardiovascular disease［J］. J Cardiovasc Transl Res, 2011, 4(2):138-144.
［25］Angert D, Berretta RM, Kubo H, et al. Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells［J］. Circ Res, 2011,108(10): 1226-1237.
［26］Urbanek K, Rota M, Cascapera S, et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival［J］. Circ Res, 2005, 97(7):663-673.
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