PP.08.11

Abstract

Objective: Monocrotaline induced pulmonary arterial hypertension is well known experimental model in rats. Undergoing processes in failing right ventricle are still not completely known. Heat shock protein 90 (Hsp90) seems to play a role in compensating mechanism alongside with caveolin-1 (CAV-1) and its phosphorylated isoform (pTyr14CAV-1). Therefore we hypothesized that levels of these proteins might be changed in right ventricle in experimentally induced pulmonary hypertension. Design and method: Group of 13 male Wistar rats was injected with monocrotaline (MON; 60 mg/kg) and 7 control rats (CON) received vehicle. Separate group of 20 (MON) and 10 (CON) rats was used for hemodynamic measurements. Animals were weighted frequently and vital functions were measured using MouseOx meter. Rats were sacrificed after 4 weeks or immediately if showing dyspnea, lethargy and significant weight loss. Results: MON-treated rats exhibited decrease in body weight when compared to controls (MON: 294 ± 9 g vs. CON: 328 ± 6, P < 0.01). There was a significant increase in the right ventricular systolic pressure (MON: 50.65 ± 6.28 vs. CON: 21.52 ± 2.49, P < 0.01). Right ventricular weight was significantly increased (MON: 0.29 ± 0.02 vs. CON: 0.17 ± 0.01, P < 0.05), whereas left ventricular weight was not significantly changed (MON: 0.69 ± 0.03 vs. CON: 0.70 ± 0.05). Expression of Hsp90 in the right ventricle of monocrotaline treated rats was significantly increased (MON: 234 ± 44 vs. CON: 100 ± 7, P < 0.05), while in left ventricle remained stable (MON: 126 ± 14 vs. CON: 100 ± 3). Caveolin-1 expression in the right ventricle of MON group was decreased (MON: 66 ± 14 vs. CON: 100 ± 9), as well as in the left ventricle (67 ± 11 vs. CON: 100 ± 23). Expression of pTyr14CAV-1 was significantly decreased in the right ventricle (MON: 48 ± 13 vs. CON: 100 ± 14, P < 0.05), while in the left ventricle was unchanged (80 ± 24 vs. CON: 100 ± 22). Conclusions: Increased level of Hsp90 along with lowered expression of CAV-1 isomers might play an important role in hypertrophied and dysfunctional right ventricle in monocrotaline induced pulmonary hypertension model.