| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Pathology, University of Washington, Seattle, Washington
Granulation tissue formation is a critical step in infarct repair, however, the kinetics of cell replication and the molecules that regulate this process are poorly understood. In uninjured mouse hearts and at 2 days post-infarction, very little DNA synthesis (measured by incorporation of a BrdU pulse) was detected in any cell type. Four days after permanent coronary occlusion, the rates of myofibroblast (smooth muscle 
-actin and BrdU double-positive) and endothelial cell (CD31 and BrdU double-positive) proliferation were 15.4 ± 1.1% and 2.9 ± 0.5%, respectively. Most proliferating cells were located at the interface of the infarct and viable tissue. By 1 week, fibroblast and endothelial cell proliferation declined to 4.1 ± 0.6% and 0.7 ± 0.1%, respectively. In the 2-week infarct, the remaining necrosis had been phagocytosed, and fibroblast and endothelial cell proliferation were <0.5%. Although leukocytes were abundant throughout infarct repair, no significant proliferation was detected at any time in cells expressing CD45 or mac-3. Infarct size at 4 days was 38 ± 5% of the left ventricle and contracted to 20 ± 4% by 4 weeks. After 4 days, the chamber dilated to four times that of the control hearts and remained so for the duration of the time course. The vascular density (per mm2) declined from 3643 ± 82 in control hearts to 2716 ± 197 at 1 week and 1010 ± 47 at 4 weeks post-myocardial infarction (MI). The average percent area occupied by vessels did not change significantly between the groups but the area/vessel (µm2) increased from 14.1 ± 0.3 in control hearts to 16.9 ± 1.9 at 1 week and 38.7 ± 7.9 at 4 weeks post-MI. These data indicate that mitogens for fibroblasts and endothelial cells peak within 4 days of infarction in the mouse heart. This provides the basis for identifying the responsible molecules and developing strategies to alter wound repair and improve cardiac function.
This article has been cited by other articles:
 |
|
 |
|
  Y. Zhang, H. Wang, A. Kovacs, E. M. Kanter, and K. A. Yamada Reduced expression of Cx43 attenuates ventricular remodeling after myocardial infarction via impaired TGF-{beta} signaling Am J Physiol Heart Circ Physiol, February 1, 2010; 298(2): H477 - H487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Beguin, V. El-Helou, J. Assimakopoulos, R. Clement, H. Gosselin, R. Brugada, L. Villeneuve, C. V. Rohlicek, D. Del Duca, N. Lapointe, et al. The phenotype and potential origin of nestin+ cardiac myocyte-like cells following infarction J Appl Physiol, October 1, 2009; 107(4): 1241 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Takemura, M. Nakagawa, H. Kanamori, S. Minatoguchi, and H. Fujiwara Benefits of reperfusion beyond infarct size limitation Cardiovasc Res, July 15, 2009; 83(2): 269 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Huang, J. Rubinstein, A. R. Prieto, L. V. Thang, and D. H. Wang Transient Receptor Potential Vanilloid Gene Deletion Exacerbates Inflammation and Atypical Cardiac Remodeling After Myocardial Infarction Hypertension, February 1, 2009; 53(2): 243 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sun, S.-H. Li, S.-M. Liu, J. Wu, R. D. Weisel, Y.-F. Zhuo, T. M. Yau, R.-K. Li, and S. S. Fazel Improvement in cardiac function after bone marrow cell thearpy is associated with an increase in myocardial inflammation Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H43 - H50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bujak, M. Dobaczewski, K. Chatila, L. H. Mendoza, N. Li, A. Reddy, and N. G. Frangogiannis Interleukin-1 Receptor Type I Signaling Critically Regulates Infarct Healing and Cardiac Remodeling Am. J. Pathol., July 1, 2008; 173(1): 57 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Fazel, L. Chen, D. Angoulvant, S.-H. Li, R. D. Weisel, A. Keating, and R.-K. Li Activation of c-kit is necessary for mobilization of reparative bone marrow progenitor cells in response to cardiac injury FASEB J, March 1, 2008; 22(3): 930 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shimazaki, K. Nakamura, I. Kii, T. Kashima, N. Amizuka, M. Li, M. Saito, K. Fukuda, T. Nishiyama, S. Kitajima, et al. Periostin is essential for cardiac healingafter acute myocardial infarction J. Exp. Med., February 18, 2008; 205(2): 295 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A.I. Virag, M. L. Rolle, J. Reece, S. Hardouin, E. O. Feigl, and C. E. Murry Fibroblast Growth Factor-2 Regulates Myocardial Infarct Repair: Effects on Cell Proliferation, Scar Contraction, and Ventricular Function Am. J. Pathol., November 1, 2007; 171(5): 1431 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cimini, S. Fazel, S. Zhuo, M. Xaymardan, H. Fujii, R. D. Weisel, and R.-K. Li c-Kit Dysfunction Impairs Myocardial Healing After Infarction Circulation, September 11, 2007; 116(11_suppl): I-77 - I-82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Makela, K. Ylitalo, S. Lehtonen, S. Dahlbacka, E. Niemela, K. Kiviluoma, J. Rimpilainen, H. Alaoja, T. Paavonen, P. Lehenkari, et al. Bone marrow derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site J. Thorac. Cardiovasc. Surg., September 1, 2007; 134(3): 565 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Morimoto, M. Takahashi, Y. Shiba, A. Izawa, H. Ise, M. Hongo, K. Hatake, K. Motoyoshi, and U. Ikeda Bone Marrow-Derived CXCR4+ Cells Mobilized by Macrophage Colony-Stimulating Factor Participate in the Reduction of Infarct Area and Improvement of Cardiac Remodeling after Myocardial Infarction in Mice Am. J. Pathol., September 1, 2007; 171(3): 755 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Drobic, R. H. Cunnington, K. M. Bedosky, J. E. Raizman, V. V. Elimban, S. G. Rattan, and I. M. C. Dixon Differential and combined effects of cardiotrophin-1 and TGF-beta1 on cardiac myofibroblast proliferation and contraction Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1053 - H1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Takagawa, Y. Zhang, M. L. Wong, R. E. Sievers, N. K. Kapasi, Y. Wang, Y. Yeghiazarians, R. J. Lee, W. Grossman, and M. L. Springer Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approaches J Appl Physiol, June 1, 2007; 102(6): 2104 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nussbaum, E. Minami, M. A. Laflamme, J. A. I. Virag, C. B. Ware, A. Masino, V. Muskheli, L. Pabon, H. Reinecke, and C. E. Murry Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response FASEB J, May 1, 2007; 21(7): 1345 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. LaFramboise, D. Scalise, P. Stoodley, S. R. Graner, R. D. Guthrie, J. A. Magovern, and M. J. Becich Cardiac fibroblasts influence cardiomyocyte phenotype in vitro Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1799 - C1808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kanamori, G. Takemura, Y. Li, H. Okada, R. Maruyama, T. Aoyama, S. Miyata, M. Esaki, A. Ogino, M. Nakagawa, et al. Inhibition of Fas-associated apoptosis in granulation tissue cells accompanies attenuation of postinfarction left ventricular remodeling by olmesartan Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2184 - H2194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Hu, J. Wang, J. Chen, R. Luo, A. He, X. Xie, and J. Li Optimal temporal delivery of bone marrow mesenchymal stem cells in rats with myocardial infarction Eur. J. Cardiothorac. Surg., March 1, 2007; 31(3): 438 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zymek, M. Bujak, K. Chatila, A. Cieslak, G. Thakker, M. L. Entman, and N. G. Frangogiannis The Role of Platelet-Derived Growth Factor Signaling in Healing Myocardial Infarcts J. Am. Coll. Cardiol., December 5, 2006; 48(11): 2315 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morimoto, M. Takahashi, A. Izawa, H. Ise, M. Hongo, P. E. Kolattukudy, and U. Ikeda Cardiac Overexpression of Monocyte Chemoattractant Protein-1 in Transgenic Mice Prevents Cardiac Dysfunction and Remodeling After Myocardial Infarction Circ. Res., October 13, 2006; 99(8): 891 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jackowski, A. Christe, M. Sonnenschein, E. Aghayev, and M. J. Thali Postmortem unenhanced magnetic resonance imaging of myocardial infarction in correlation to histological infarction age characterization Eur. Heart J., October 2, 2006; 27(20): 2459 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Jarvis, M. T. Rademaker, L. J. Ellmers, M. J. Currie, J. L. McKenzie, B. R. Palmer, C. M. Frampton, A. M. Richards, and V. A. Cameron Comparison of infarct-derived and control ovine cardiac myofibroblasts in culture: response to cytokines and natriuretic peptide receptor expression profiles. Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1952 - H1958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mollmann, H. M. Nef, S. Kostin, C. von Kalle, I. Pilz, M. Weber, J. Schaper, C. W. Hamm, and A. Elsasser Bone marrow-derived cells contribute to infarct remodelling Cardiovasc Res, September 1, 2006; 71(4): 661 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, T. Esaki, D. Sumi, T. Mukherjee, A. Iguchi, and G. Chaudhuri Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism PNAS, July 5, 2006; 103(27): 10485 - 10490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kanellakis, N. J. Slater, X.-J. Du, A. Bobik, and D. J. Curtis Granulocyte colony-stimulating factor and stem cell factor improve endogenous repair after myocardial infarction Cardiovasc Res, April 1, 2006; 70(1): 117 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Vanhoutte, M. Schellings, Y. Pinto, and S. Heymans Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial window Cardiovasc Res, February 15, 2006; 69(3): 604 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, A. S. Pachori, C. A. Ward, J. P. Davis, M. Gnecchi, D. Kong, L. Zhang, J. Murduck, S.-F. Yet, M. A. Perrella, et al. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function FASEB J, February 1, 2006; 20(2): 207 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. van den Bos, B. M. E. Mees, M. C. de Waard, R. de Crom, and D. J. Duncker A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1291 - H1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Small, P. W. F. Hadoke, I. Sharif, A. R. Dover, D. Armour, C. J. Kenyon, G. A. Gray, and B. R. Walker Preventing local regeneration of glucocorticoids by 11{beta}-hydroxysteroid dehydrogenase type 1 enhances angiogenesis PNAS, August 23, 2005; 102(34): 12165 - 12170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tamaoki, K. Imanaka-Yoshida, K. Yokoyama, T. Nishioka, H. Inada, M. Hiroe, T. Sakakura, and T. Yoshida Tenascin-C Regulates Recruitment of Myofibroblasts during Tissue Repair after Myocardial Injury Am. J. Pathol., July 1, 2005; 167(1): 71 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Dewald, P. Zymek, K. Winkelmann, A. Koerting, G. Ren, T. Abou-Khamis, L. H. Michael, B. J. Rollins, M. L. Entman, and N. G. Frangogiannis CCL2/Monocyte Chemoattractant Protein-1 Regulates Inflammatory Responses Critical to Healing Myocardial Infarcts Circ. Res., April 29, 2005; 96(8): 881 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kinnaird, E. Stabile, M. S. Burnett, and S. E. Epstein Bone Marrow-Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences Circ. Res., August 20, 2004; 95(4): 354 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mayorga, N. Bahi, M. Ballester, J. X. Comella, and D. Sanchis Bcl-2 Is a Key Factor for Cardiac Fibroblast Resistance to Programmed Cell Death J. Biol. Chem., August 13, 2004; 279(33): 34882 - 34889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Rossow, E. Minami, E. G. Chase, C. E. Murry, and L.F. Santana NFATc3-Induced Reductions in Voltage-Gated K+ Currents After Myocardial Infarction Circ. Res., May 28, 2004; 94(10): 1340 - 1350. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
