Inhibition of apoptosis signal-regulating kinase 1 ameliorates left ventricular dysfunction by reducing hypertrophy and fibrosis in a rat model of cardiorenal syndrome
Feby Savira, Bing H Wang, Amanda J Edgley, Beat M Jucker, Robert N Willette, Henry Krum, Darren J Kelly, Andrew R Kompa
International Journal of Cardiology | Elsevier | Published : 2020
BACKGROUND: Cardiorenal syndrome (CRS) is a major health burden worldwide in need of novel therapies, as current treatments remain suboptimal. The present study assessed the therapeutic potential of apoptosis signal-regulating kinase 1 (ASK1) inhibition in a rat model of CRS. METHODS: Adult male Sprague-Dawley rats underwent surgery for myocardial infarction (MI) (week 0) followed by 5/6 subtotal nephrectomy (STNx) at week 4 to induce to induce a combined model of heart and kidney dysfunction. At week 6, MI + STNx animals were randomized to receive either 0.5% carboxymethyl cellulose (Vehicle, n = 15, Sham = 10) or G226 (15 mg/kg daily, n = 11). Cardiac and renal function was assessed by ..View full abstract
Awarded by National Health and Medical Research Council of Australia
This research was supported by National Health and Medical Research Council of Australia (Program Grants 1092642 and Project Grant 1087355). FS is supported by Monash International Postgraduate Research Scholarship and Monash Graduate Scholarship.