© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis
UCSD Med. Ctr. 8412, Department of Medicine, 200 West Arbor St., San Diego, CA 92103-8412, USA
* Corresponding author. Tel.: +1-619-543-3903; fax: +1-619-543-3306 fvillarr{at}ucsd.edu
The cardiac fibroblast is the most abundant cell type present in the myocardium and is mainly responsible for the deposition of extracellular matrix (ECM). Important components of cardiac ECM include structural and adhesive proteins such as collagen and fibronectin. Excess deposition of cardiac ECM (fibrosis) has been associated with the pathophysiological mechanical overload of the heart. Therefore, the role of cardiac fibroblasts in "sensing", "integrating" and "responding" to mechanical stimuli is of great interest. The development of in vitro strain apparatuses has allowed scientists to investigate the effects of mechanical stimuli on cardiac fibroblast function. Cardiac fibroblasts express ECM receptors (integrins) which couple mechanical stimuli to functional responses. Mechanical stimulation of cardiac fibroblasts has been shown to result in activation of various signal transduction pathways. The application of defined mechanical stimuli to cultured cardiac fibroblasts has been associated with ECM gene expression, growth factor production, release and/or bioactivity as well as collagenase activity. Ultimately, for fibrosis to develop the overproduction of ECM must overcome any associated increases in collagenase activity. Mechanically induced upregulation of ECM production may follow direct or indirect pathways through the autocrine or paracrine action of growth factors. Given the complex nature of the interstitial milieu of the working heart, additional research is needed to further our understanding of the roles that mechanical stimuli play in excess deposition of myocardial ECM.
KEYWORDS Angiotensin; Cell culture/isolation; Extracellular matrix; Fibrosis; Mechanotransduction
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Snider, K. N. Standley, J. Wang, M. Azhar, T. Doetschman, and S. J. Conway Origin of Cardiac Fibroblasts and the Role of Periostin Circ. Res., November 6, 2009; 105(10): 934 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. C. Chan, P. D. Arora, P. Bozavikov, and C. A. McCulloch FAK, PIP5KI{gamma} and gelsolin cooperatively mediate force-induced expression of {alpha}-smooth muscle actin J. Cell Sci., August 1, 2009; 122(15): 2769 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Jobling, A. Gentle, R. Metlapally, B. J. McGowan, and N. A. McBrien Regulation of Scleral Cell Contraction by Transforming Growth Factor-{beta} and Stress: COMPETING ROLES IN MYOPIC EYE GROWTH J. Biol. Chem., January 23, 2009; 284(4): 2072 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.S. Brizzolara, J. Killeen, and J. Urschitz Gene expression profile in pelvic organ prolapse Mol. Hum. Reprod., January 1, 2009; 15(1): 59 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Huang, C. Yang, Y. Wang, Y. Liao, and K. Huang PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR{gamma} in cardiac fibroblasts Cardiovasc Res, January 1, 2009; 81(1): 98 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Garcia-Bolao, B. Lopez, A. Macias, J. J. Gavira, P. Azcarate, and J. Diez Impact of collagen type I turnover on the long-term response to cardiac resynchronization therapy Eur. Heart J., April 1, 2008; 29(7): 898 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Burstein and S. Nattel Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 802 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Beeri, C. Yosefy, J. L. Guerrero, F. Nesta, S. Abedat, M. Chaput, F. del Monte, M. D. Handschumacher, R. Stroud, S. Sullivan, et al. Mitral regurgitation augments post-myocardial infarction remodeling failure of hypertrophic compensation. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 476 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Husse, W. Briest, L. Homagk, G. Isenberg, and M. Gekle Cyclical mechanical stretch modulates expression of collagen I and collagen III by PKC and tyrosine kinase in cardiac fibroblasts Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1898 - R1907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Swaney, H. H. Patel, U. Yokoyama, N. C. Lai, M. Spellman, P. A. Insel, and D. M. Roth Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3216 - H3220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Spruill, A. S. Lowry, R. E. Stroud, C. E. Squires, I. M. Mains, E. C. Flack, C. Beck, J. S. Ikonomidis, A. J. Crumbley, P. J. McDermott, et al. Membrane-type-1 matrix metalloproteinase transcription and translation in myocardial fibroblasts from patients with normal left ventricular function and from patients with cardiomyopathy Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1362 - C1373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Hu, L. K. Landeen, N. Aroonsakool, and W. R. Giles An analysis of the effects of stretch on IGF-I secretion from rat ventricular fibroblasts Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H677 - H683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Zhao, C. Laschinger, P. Arora, K. Szaszi, A. Kapus, and C. A. McCulloch Force activates smooth muscle {alpha}-actin promoter activity through the Rho signaling pathway J. Cell Sci., May 15, 2007; 120(10): 1801 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Henderson, N. Tyagi, A. Ovechkin, G. K. Kartha, K. S. Moshal, and S. C. Tyagi Oxidative remodeling in pressure overload induced chronic heart failure Eur J Heart Fail, May 1, 2007; 9(5): 450 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Ryan, E. C. Rothstein, I. Aban, J. A. Tallaj, A. Husain, P. A. Lucchesi, and L. J. Dell'Italia Left Ventricular Eccentric Remodeling and Matrix Loss Are Mediated by Bradykinin and Precede Cardiomyocyte Elongation in Rats With Volume Overload J. Am. Coll. Cardiol., February 20, 2007; 49(7): 811 - 821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Poobalarahi, C. F. Baicu, and A. D. Bradshaw Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2924 - H2932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gupta and K. J. Grande-Allen Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells Cardiovasc Res, December 1, 2006; 72(3): 375 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Podgorska, K. Kocbuch, M. Grden, A. Szutowicz, and T. Pawelczyk Reduced ability to release adenosine by diabetic rat cardiac fibroblasts due to altered expression of nucleoside transporters J. Physiol., October 1, 2006; 576(1): 179 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Ku, P. H. Johnson, P. Batten, P. Sarathchandra, R. C. Chambers, P. M. Taylor, M. H. Yacoub, and A. H. Chester Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch Cardiovasc Res, August 1, 2006; 71(3): 548 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Park, S. M. Ward, J. S. Desgrosellier, S. P. Georgescu, A. G. Papageorge, X. Zhuang, J. V. Barnett, and J. B. Galper Transforming Growth Factor beta Regulates the Expression of the M2 Muscarinic Receptor in Atrial Myocytes via an Effect on RhoA and p190RhoGAP J. Biol. Chem., July 21, 2006; 281(29): 19995 - 20002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakamura, K. Matsumoto, S. Mizuno, Y. Sawa, H. Matsuda, and T. Nakamura Hepatocyte growth factor prevents tissue fibrosis, remodeling, and dysfunction in cardiomyopathic hamster hearts Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2131 - H2139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Boateng, S. S. Lateef, W. Mosley, T. J. Hartman, L. Hanley, and B. Russell RGD and YIGSR synthetic peptides facilitate cellular adhesion identical to that of laminin and fibronectin but alter the physiology of neonatal cardiac myocytes Am J Physiol Cell Physiol, January 1, 2005; 288(1): C30 - C38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Camelliti, T. K. Borg, and P. Kohl Structural and functional characterisation of cardiac fibroblasts Cardiovasc Res, January 1, 2005; 65(1): 40 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Watanabe, Y. Nagashio, H. Asaumi, Y. Nomiyama, M. Taguchi, M. Tashiro, Y. Kihara, H. Nakamura, and M. Otsuki Pressure activates rat pancreatic stellate cells Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1175 - G1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Moriwaki, A. Stempien-Otero, M. Kremen, A. E. Cozen, and D. A. Dichek Overexpression of Urokinase by Macrophages or Deficiency of Plasminogen Activator Inhibitor Type 1 Causes Cardiac Fibrosis in Mice Circ. Res., September 17, 2004; 95(6): 637 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S Ross Molecular and mechanical synergy: cross-talk between integrins and growth factor receptors Cardiovasc Res, August 15, 2004; 63(3): 381 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. KJAeR Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading Physiol Rev, April 1, 2004; 84(2): 649 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, H. Chen, A. Seth, and C. A. McCulloch Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1871 - H1881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H Freed, A. M Borowiec, T. Angelovska, and I. M.C Dixon Induction of protein synthesis in cardiac fibroblasts by cardiotrophin-1: integration of multiple signaling pathways Cardiovasc Res, November 1, 2003; 60(2): 365 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R Strauch Building better blood vessels: new insight on the molecular control of arteriogenesis Cardiovasc Res, September 1, 2003; 59(3): 532 - 533. [Full Text] [PDF]
|
|
|
|
|
|
I. P. Uray, J. H. Connelly, O.H. Frazier, H. Taegtmeyer, and P. J.A. Davies Mechanical unloading increases caveolin expression in the failing human heart Cardiovasc Res, July 1, 2003; 59(1): 57 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fluck, M. Chiquet, S. Schmutz, M.-H. Mayet-Sornay, and D. Desplanches Reloading of atrophied rat soleus muscle induces tenascin-C expression around damaged muscle fibers Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R792 - R801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Cohen, D. S. Park, S. E. Woodman, T. M. Williams, M. Chandra, J. Shirani, A. Pereira de Souza, R. N. Kitsis, R. G. Russell, L. M. Weiss, et al. Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts Am J Physiol Cell Physiol, February 1, 2003; 284(2): C457 - C474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Spinale Bioactive Peptide Signaling Within the Myocardial Interstitium and the Matrix Metalloproteinases Circ. Res., December 13, 2002; 91(12): 1082 - 1084. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Sussman, A. McCulloch, and T. K. Borg Dance Band on the Titanic: Biomechanical Signaling in Cardiac Hypertrophy Circ. Res., November 15, 2002; 91(10): 888 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Frungieri, S. Weidinger, V. Meineke, F. M. Kohn, and A. Mayerhofer Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARgamma : Possible relevance to human fibrotic disorders PNAS, November 12, 2002; 99(23): 15072 - 15077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M Aartsen, M. P Schuijt, A.H.J. Danser, M. J.A.P Daemen, and J. F.M Smits The role of locally expressed angiotensin converting enzyme in cardiac remodeling after myocardial infarction in mice Cardiovasc Res, November 1, 2002; 56(2): 205 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Lavelin, N. Meiri, M. Einat, O. Genina, and M. Pines Mechanical strain regulation of the chicken glypican-4 gene expression in the avian eggshell gland Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R853 - R861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Park, S. E. Woodman, W. Schubert, A. W. Cohen, P. G. Frank, M. Chandra, J. Shirani, B. Razani, B. Tang, L. A. Jelicks, et al. Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype Am. J. Pathol., June 1, 2002; 160(6): 2207 - 2217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Stoica, D. K. Satchithananda, J. Dunning, and S. R. Large Two-decade analysis of cardiac storage for transplantation Eur. J. Cardiothorac. Surg., October 1, 2001; 20(4): 792 - 798. [Abstract] [Full Text] [PDF]
|
|