Myocyte proliferation in end-stage cardiac failure in humans - PubMed (original) (raw)
Myocyte proliferation in end-stage cardiac failure in humans
J Kajstura et al. Proc Natl Acad Sci U S A. 1998.
Abstract
Introduced several decades ago, the dogma persists that cardiac myocytes are terminally differentiated cells and that division of muscle cells is impossible in the adult heart. More recently, nuclear mitotic divisions in myocytes occasionally were seen, but those observations were challenged on the assumption that the rate of cell proliferation was inconsequential for actual tissue regeneration. Moreover, mitoses were never detected in normal myocardium. However, the analysis of routine histologic preparations constituted the basis for the belief that myocytes were unable to reenter the cell cycle and divide, ignoring the limitations of these techniques. We report here by confocal microscopy that 14 myocytes per million were in mitosis in control human hearts. A nearly 10-fold increase in this parameter was measured in end-stage ischemic heart disease (152 myocytes per million) and in idiopathic dilated cardiomyopathy (131 myocytes per million). Because the left ventricle contains 5.8 x 10(9) myocytes, these mitotic indices imply that 81.2 x 10(3), 882 x 10(3), and 760 x 10(3) myocytes were in mitosis in the entire ventricular myocardium of control hearts and hearts affected by ischemic and idiopathic dilated cardiomyopathy, respectively. Additionally, mitosis lasts less than 1 hr, suggesting that large numbers of myocytes can be formed in the nonpathologic and pathologic heart with time. Evidence of cytokinesis in myocytes was obtained, providing unequivocal proof of myocyte proliferation.
Figures
Figure 1
(On the opposite page) Left ventricular myocardial section of a patient affected by end-stage dilated cardiomyopathy. Large field area illustrated by propidium iodide labeling only (green; A) and by a combination of propidium iodide and α-sarcomeric actin staining of the myocyte cytoplasm (red; B). Arrowhead indicates a myocyte nucleus in metaphase, and arrows indicate a myocyte at completion of cytokinesis. Myocyte cytokinesis is shown at higher magnification in C by a combination of propidium iodide and α-sarcomeric actin antibody staining (green and red, respectively). (D_–_F) Three mitotic figures in the center of myocytes corresponding to a patient with ischemic cardiomyopathy (D), dilated cardiomyopathy (E), and control left ventricle (F). Staining in D_–_F consists of a combination of propidium iodide and α-sarcomeric actin antibody. The punctate red staining in D corresponds to lipofuscin. (G) Two interstitial cell nuclei (arrow and arrowhead) (green), one of which is in mitosis (arrowhead). The cytoplasm of these nonmyocytes is not visible because it is not stained by α-sarcomeric actin antibody. (H) A mitotic figure in a myocyte from a patient with dilated myopathy is apparent (arrowhead); two interstitial cell nuclei (green) also are noted (arrows). These interstitial cells are not α-sarcomeric actin positive. (I) A mitotic figure in a center of a myocyte in which a large area of undifferentiated cytoplasm (negative to α-sarcomeric actin staining) surrounds the dividing nucleus is illustrated (patient with ischemic cardiomyopathy). (J_–_L) Patient with dilated cardiomyopathy. Two nuclei by propidium iodide (J, green), myocyte cytoplasm labeled by α-sarcomeric actin (K, red), and a combination of these two images (L). Note the myocyte nucleus in late telophase (arrows) and the nondividing interstitial cell nucleus (arrowheads). Magnifications: (A and B) ×700; (C) ×1,300; (D) ×2,700; (E, F, H, and I) ×1,500; (G) ×1,200; (J_–_L) ×1,600.
Figure 2
Mitotic index in myocytes from control hearts (Controls), and hearts affected by ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Results are presented as means ± SD. ∗, P < 0.00l. Controls: n = 9; IC, n = 12; IDC, n = l5.
Similar articles
- Myocyte nuclear mitotic division and programmed myocyte cell death characterize the cardiac myopathy induced by rapid ventricular pacing in dogs.
Liu Y, Cigola E, Cheng W, Kajstura J, Olivetti G, Hintze TH, Anversa P. Liu Y, et al. Lab Invest. 1995 Dec;73(6):771-87. Lab Invest. 1995. PMID: 8558838 - Nuclear size of myocardial cells in end-stage cardiomyopathies.
Yan SM, Finato N, Di Loreto C, Beltrami CA. Yan SM, et al. Anal Quant Cytol Histol. 1999 Apr;21(2):174-80. Anal Quant Cytol Histol. 1999. PMID: 10560488 - End-stage cardiac failure in humans is coupled with the induction of proliferating cell nuclear antigen and nuclear mitotic division in ventricular myocytes.
Quaini F, Cigola E, Lagrasta C, Saccani G, Quaini E, Rossi C, Olivetti G, Anversa P. Quaini F, et al. Circ Res. 1994 Dec;75(6):1050-63. doi: 10.1161/01.res.75.6.1050. Circ Res. 1994. PMID: 7955143 - Myocyte growth and cardiac repair.
Anversa P, Leri A, Kajstura J, Nadal-Ginard B. Anversa P, et al. J Mol Cell Cardiol. 2002 Feb;34(2):91-105. doi: 10.1006/jmcc.2001.1506. J Mol Cell Cardiol. 2002. PMID: 11851350 Review. - Plasticity of the pathologic heart.
Anversa P. Anversa P. Ital Heart J. 2000 Feb;1(2):91-5. Ital Heart J. 2000. PMID: 10730607 Review.
Cited by
- A review on regulation of DNA methylation during post-myocardial infarction.
Han W, Wang W, Wang Q, Maduray K, Hao L, Zhong J. Han W, et al. Front Pharmacol. 2024 Feb 13;15:1267585. doi: 10.3389/fphar.2024.1267585. eCollection 2024. Front Pharmacol. 2024. PMID: 38414735 Free PMC article. Review. - Cardiomyocyte Ploidy, Metabolic Reprogramming and Heart Repair.
Elia A, Mohsin S, Khan M. Elia A, et al. Cells. 2023 Jun 7;12(12):1571. doi: 10.3390/cells12121571. Cells. 2023. PMID: 37371041 Free PMC article. Review. - Cardiomyocyte nuclear remodeling after mechanical unloading.
Luo J, Farris SD, Helterline D, Stempien-Otero A. Luo J, et al. Am J Physiol Heart Circ Physiol. 2023 Aug 1;325(2):H244-H251. doi: 10.1152/ajpheart.00545.2022. Epub 2023 May 19. Am J Physiol Heart Circ Physiol. 2023. PMID: 37204870 Free PMC article. - The Roles of Macrophages in Heart Regeneration and Repair After Injury.
Gao Y, Qian N, Xu J, Wang Y. Gao Y, et al. Front Cardiovasc Med. 2021 Oct 25;8:744615. doi: 10.3389/fcvm.2021.744615. eCollection 2021. Front Cardiovasc Med. 2021. PMID: 34760943 Free PMC article. Review. - Gene expression variability in human and chimpanzee populations share common determinants.
Fair BJ, Blake LE, Sarkar A, Pavlovic BJ, Cuevas C, Gilad Y. Fair BJ, et al. Elife. 2020 Oct 21;9:e59929. doi: 10.7554/eLife.59929. Elife. 2020. PMID: 33084571 Free PMC article.
References
- Chien K R. Am J Physiol. 1995;269:H755–H766. - PubMed
- Linzbach A J. Am J Cardiol. 1960;5:370–382. - PubMed
- Astorri E, Bolognesi R, Colla B, Chizzola A, Visioli O. J Mol Cell Cardiol. 1977;9:763–775. - PubMed
- Quaini F, Cigola E, Lagrasta C, Saccani G, Quaini E, Rossi C, Olivetti G, Anversa P. Circ Res. 1994;75:1050–1063. - PubMed
Publication types
MeSH terms
Grants and funding
- HL-43023/HL/NHLBI NIH HHS/United States
- R01 HL038132/HL/NHLBI NIH HHS/United States
- P01 HL043023/HL/NHLBI NIH HHS/United States
- R01 HL039902/HL/NHLBI NIH HHS/United States
- HL-38132/HL/NHLBI NIH HHS/United States
- HL-39902/HL/NHLBI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources