This Article Full Text Full Text (PDF) All Versions of this Article: 42/4/737    most recent 01.HYP.0000083511.91817.B1v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iglarz, M. Articles by Schiffrin, E. L. Search for Related Content PubMed PubMed Citation Articles by Iglarz, M. Articles by Schiffrin, E. L. Related Collections Remodeling Heart failure - basic studies Hypertension - basic studies Hypertrophy

(Hypertension. 2003;42:737.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Peroxisome Proliferator-Activated Receptor- and Receptor- Activators Prevent Cardiac Fibrosis in Mineralocorticoid-Dependent Hypertension

Marc Iglarz; Rhian M. Touyz; Emilie C. Viel; Pierre Paradis; Farhad Amiri; Quy N. Diep; Ernesto L. Schiffrin

From CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.

Correspondence to Ernesto L. Schiffrin, MD, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, Canada H2W 1R7. E-mail schiffe{at}ircm.qc.ca

Peroxisome proliferator-activated receptor (PPAR) activation may prevent cardiac hypertrophy and inhibit production of endothelin-1 (ET-1), a hypertrophic agent. The aim of this in vivo study was to investigate the effects of PPAR activators on cardiac remodeling in DOCA-salt rats, a model overexpressing ET-1. Unilaterally nephrectomized 16-week-old Sprague-Dawley rats (Uni-Nx) were randomly divided into 4 groups: control rats, DOCA-salt, DOCA-salt+rosiglitazone (PPAR- activator, 5 mg/kg per day), and DOCA-salt+fenofibrate (PPAR- activator, 100 mg/kg per day). After 3 weeks of treatment, mean arterial blood pressure was significantly increased in DOCA-salt by 36 mm Hg. Mean arterial blood pressure was normalized by coadministration of rosiglitazone but not by fenofibrate. Both PPAR activators prevented cardiac fibrosis and abrogated the increase in prepro–ET-1 mRNA content in the left ventricle of DOCA-salt rats. Coadministration of rosiglitazone or fenofibrate failed to prevent thickening of left ventricle (LV) walls as measured by echocardiography and the increase in atrial natriuretic peptide mRNA levels. However, rosiglitazone and fenofibrate prevented the decrease in LV internal diameter and thus concentric remodeling of the LV found in DOCA-salt rats. Taken together, these data indicate a modulatory role of PPAR activators on cardiac remodeling in mineralocorticoid-induced hypertension, in part associated with decreased ET-1 production.

Key Words: endothelin • remodeling • fibrosis • hypertension, mineralocorticoid • collagen • hypertrophy

This article has been cited by other articles:

				N. Koleganova, G. Piecha, E. Ritz, and M.-L. Gross Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats Nephrol. Dial. Transplant., October 1, 2008; (2008) gfn549v1. [Abstract] [Full Text] [PDF]

				I. Kuipers, P. van der Harst, G. Navis, L. van Genne, F. Morello, W. H. van Gilst, D. J. van Veldhuisen, and R. A. de Boer Nuclear Hormone Receptors as Regulators of the Renin-Angiotensin-Aldosterone System Hypertension, June 1, 2008; 51(6): 1442 - 1448. [Full Text] [PDF]

				K. M. Tordjman, C. F. Semenkovich, T. Coleman, R. Yudovich, S. Bak, E. Osher, M. Vechoropoulos, and N. Stern Absence of Peroxisome Proliferator-Activated Receptor-{alpha} Abolishes Hypertension and Attenuates Atherosclerosis in the Tsukuba Hypertensive Mouse Hypertension, November 1, 2007; 50(5): 945 - 951. [Abstract] [Full Text] [PDF]

				C. Yagil and Y. Yagil Peroxisome Proliferator-Activated Receptor {alpha}: Friend or Foe? Hypertension, November 1, 2007; 50(5): 847 - 850. [Full Text] [PDF]

				N. K. LeBrasseur, T.-A. S. Duhaney, D. S. De Silva, L. Cui, P. C. Ip, L. Joseph, and F. Sam Effects of Fenofibrate on Cardiac Remodeling in Aldosterone-Induced Hypertension Hypertension, September 1, 2007; 50(3): 489 - 496. [Abstract] [Full Text] [PDF]

				B. E.J. Teunissen, P. J.H. Smeets, P. H.M. Willemsen, L. J. De Windt, G. J. Van der Vusse, and M. Van Bilsen Activation of PPAR{delta} inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts Cardiovasc Res, August 1, 2007; 75(3): 519 - 529. [Abstract] [Full Text] [PDF]

				A. Shiroshita-Takeshita, B. J.J.M. Brundel, B. Burstein, T.-K. Leung, H. Mitamura, S. Ogawa, and S. Nattel Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure Cardiovasc Res, April 1, 2007; 74(1): 75 - 84. [Abstract] [Full Text] [PDF]

				P. A. Sarafidis and G. L. Bakris Insulin and Endothelin: An Interplay Contributing to Hypertension Development? J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 379 - 385. [Abstract] [Full Text] [PDF]

				V. Subramanian, P. Krishnamurthy, K. Singh, and M. Singh Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic mice Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H673 - H683. [Abstract] [Full Text] [PDF]

				P. Rocic, B. Rezk, and P. A. Lucchesi PPAR-{gamma} agonists decrease hyperhomcysteinemia and cardiac dysfunction: new hope for ailing diabetic hearts? Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H26 - H28. [Full Text] [PDF]

				M. J. Goikoetxea, J. Beaumont, A. Gonzalez, B. Lopez, R. Querejeta, M. Larman, and J. Diez Altered cardiac expression of peroxisome proliferator-activated receptor-isoforms in patients with hypertensive heart disease Cardiovasc Res, March 1, 2006; 69(4): 899 - 907. [Abstract] [Full Text] [PDF]

				K. K. Koh, M. J. Quon, S. H. Han, W.-J. Chung, J. Y. Ahn, J.-a Kim, Y. Lee, and E. K. Shin Additive Beneficial Effects of Fenofibrate Combined With Candesartan in the Treatment of Hypertriglyceridemic Hypertensive Patients Diabetes Care, February 1, 2006; 29(2): 195 - 201. [Abstract] [Full Text] [PDF]

				R. A. Ahokas, Y. Sun, S. K. Bhattacharya, I. C. Gerling, and K. T. Weber Aldosteronism and a Proinflammatory Vascular Phenotype: Role of Mg2+, Ca2+, and H2O2 in Peripheral Blood Mononuclear Cells Circulation, January 4, 2005; 111(1): 51 - 57. [Abstract] [Full Text] [PDF]

				F. J. Villarreal and J. Asbun Peroxisome Proliferator-Activated Receptors Ligands, Oxidative Stress, and Cardiac Fibroblast Extracellular Matrix Turnover Hypertension, November 1, 2004; 44(5): 621 - 622. [Full Text] [PDF]

				S. Wakino, K. Hayashi, T. Kanda, S. Tatematsu, K. Homma, K. Yoshioka, I. Takamatsu, and T. Saruta Peroxisome Proliferator-Activated Receptor {gamma} Ligands Inhibit Rho/Rho Kinase Pathway by Inducing Protein Tyrosine Phosphatase SHP-2 Circ. Res., September 3, 2004; 95(5): e45 - e55. [Abstract] [Full Text] [PDF]

				T. Ogata, T. Miyauchi, S. Sakai, M. Takanashi, Y. Irukayama-Tomobe, and I. Yamaguchi Myocardial fibrosis and diastolic dysfunction in deoxycorticosterone acetate-salt hypertensive rats is ameliorated by the peroxisome proliferator-activated receptor-alpha activator fenofibrate, partly by suppressing inflammatory responses associated with the nuclear factor-kappa-b pathway J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1481 - 1488. [Abstract] [Full Text] [PDF]

				K. T. Weber From Inflammation to Fibrosis: A Stiff Stretch of Highway Hypertension, April 1, 2004; 43(4): 716 - 719. [Full Text] [PDF]