Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction
Sih Min Tan, Yuan Zhang, Kim A Connelly, Richard E Gilbert, Darren J Kelly
American Journal of Physiology - Heart and Circulatory Physiology | AMER PHYSIOLOGICAL SOC | Published : 2010
Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results in cardiac dysfunction and ultimately heart failure and death. Transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of cardiac remodeling following MI. We thus aimed to inhibit TGF-beta signaling using a novel orally active TGF-beta type I receptor [activin receptor-like kinase 5 (ALK5)] inhibitor (GW788388) to attenuate left ventricular remodeling and cardiac dysfunction in a rat model of MI. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce experimental MI and then were randomized to receive..View full abstract
Awarded by National Health and Medical Research Council of Australia
This work was supported by funding from GlaxoSmithKline ( to R. E. Gilbert). K. A. Connelly was supported by a Heart and Stroke Foundation Canada Phase 1 clinician scientist award, a Tailored Advance Collaborative Training in Cardiovascular Sciences scholarship (Canada), and a National Health and Medical Research Council of Australia Neil Hamilton Fairley scholarship (ID 440712).