Poly (ADP-ribose) polymerase-1: An emerging target in right ventricle dysfunction associated with pulmonary hypertension

Publication date: Available online 3 December 2014 Source:Pulmonary Pharmacology & Therapeutics Author(s): Gurpreet Kaur , Neetu Singh , Poorella Lingeshwar , Hefazat H. Siddiqui , Kashif Hanif Recently, inhibition of poly (ADP-ribose) polymerase-1 (PARP1) was shown to be protective in experimental pulmonary hypertension (PH) and prevented right ventricular hypertrophy (RVH) associated with it. However, molecular mechanism behind cardioprotection by PARP1 inhibition in PH still needs detailed exploration. Therefore, effect of inhibition of PARP1 on the right ventricle (RV) dysfunction was studied in monocrotaline (MCT) induced PH model. Following a single dose administration of MCT (60 mg/kg, s.c.), male Sprague-Dawley rats were treated with PARP1 inhibitor 1,5-Isoquinolinediol (ISO, 3 mg/kg, i.p.) for 35 days for preventive study and from day 21–35 for curative study. RV pressure (RVP) and RVH were measured after 35 days. Histophathological studies, PARP1 activity, mRNA and protein expression were studied in isolated RV. Oxidative and nitosative stress, inflammation and Matrix metalloproteinases (MMPs)/Tissue inhibitor of metalloproteinase 2 (TIMP2) were also assessed. Mitochondrial dysfunction was studied by mitochondrial membrane permeability and estimation of Nicotinamide adenine dinucleotide (NAD) and Adenosine triphosphate (ATP). Apoptosis in RV was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity ...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research