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Transforming growth factor-beta blockade down-regulates the renin-angiotensin system and modifies cardiac remodeling after myocardial infarction.
Ellmers, Leigh J; Scott, Nicola J A; Medicherla, Satyanarayana; Pilbrow, Anna P; Bridgman, Paul G; Yandle, Timothy G; Richards, A Mark; Protter, Andrew A; Cameron, Vicky A.
Afiliación
  • Ellmers LJ; Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch 8140, New Zealand. leigh.ellmers@chmeds.ac.nz
Endocrinology ; 149(11): 5828-34, 2008 Nov.
Article en En | MEDLINE | ID: mdl-18653707
After myocardial infarction (MI), the heart may undergo progressive ventricular remodeling, resulting in a deterioration of cardiac function. TGF-beta is a key cytokine that both initiates and terminates tissue repair, and its sustained production underlies the development of tissue fibrosis, particularly after MI. We investigated the effects of a novel orally active specific inhibitor of the TGF-beta receptor 1 (SD-208) in an experimental model of MI. Mice underwent ligation of the left coronary artery to induce MI and were subsequently treated for 30 d after infarction with either SD-208 or a vehicle control. Blockade of TGF-beta signaling reduced mean arterial pressure in all groups. SD-208 treatment after MI resulted in a trend for reduced ventricular and renal gene expression of TGF-beta-activated kinase-1 (a downstream modulator of TGF-beta signaling) and a significant decrease in collagen 1, in association with a marked decrease in cardiac mass. Post-MI SD-208 treatment significantly reduced circulating levels of plasma renin activity as well as down-regulating the components of the cardiac and renal renin-angiotensin system (angiotensinogen, angiotensin converting enzyme, and angiotensin II type I receptor). Our findings indicate that blockade of the TGF-beta signaling pathway results in significant amelioration of deleterious cardiac remodeling after infarction.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pteridinas / Sistema Renina-Angiotensina / Factor de Crecimiento Transformador beta / Remodelación Ventricular / Infarto del Miocardio Tipo de estudio: Prognostic_studies Idioma: En Revista: Endocrinology Año: 2008 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pteridinas / Sistema Renina-Angiotensina / Factor de Crecimiento Transformador beta / Remodelación Ventricular / Infarto del Miocardio Tipo de estudio: Prognostic_studies Idioma: En Revista: Endocrinology Año: 2008 Tipo del documento: Article