Abstract 176: Administration of a Caveolin-1 Mimetic Peptide Rescues the Cardiac and Pulmonary Abnormalities Observed in Cav-1 KO mice
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Abstract
Introduction: Caveolins (Cav), the principal structural proteins of the caveolar domain, have been implicated in the development of cardiac hypertrophy, pulmonary hypertension (PH) and lung remodeling. Mice with homozygous deletion of the Cav-1 gene display cardiac hypertrophy and pulmonary abnormalities characterized by thickened alveolar septa, hypercellularity and PH. In vivo administration of a cell-permeable Cav-1 mimetic peptide was previously shown to prevent the development of monocrotaline-induced pulmonary artery medial hypertrophy, PH and right ventricular hypertrophy in rats. Whether administration of such a Cav-1 peptide could rescue the cardio-pulmonary defects observed in Cav-1 KO mice remains unknown.
Methods and Results: Three week-old wild-type and Cav-1 KO mice were randomly assigned to receive a daily intraperitoneal injection of either saline, penetratin alone (AP, 2.5 mg/kg/d) or a peptide consisting of the Cav-1 scaffolding domain coupled to penetratin (AP-Cav, 2.5 mg/kg/d) for five weeks. Cav-1 KO mice receiving either saline or AP alone developed PH with respective RV systolic pressures (RVSP) of 35.6 ± 2.0 mmHg and 34.8 ± 1.7 mmHg. Daily administration of AP-Cav to Cav-1 KO mice significantly reduced the RVSP to 28.1 ± 1.5 mmHg. Cav-1 KO mice receiving saline or AP alone also displayed both left and right ventricular hypertrophy, which were prevented by daily delivery of AP-Cav. Lungs of Cav-1 KO mice receiving saline or AP alone further showed pulmonary artery medial hypertrophy, thickened alveolar septa and hypercellularity, which were all significantly improved by daily administration of AP-Cav.
Conclusions: Administration of a cell-permeable Cav-1-mimetic peptide (AP-Cav) to Cav-1 KO mice reduces the development of pulmonary artery medial hypertrophy, PH and cardiac hypertrophy.
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- Abstract 176: Administration of a Caveolin-1 Mimetic Peptide Rescues the Cardiac and Pulmonary Abnormalities Observed in Cav-1 KO miceJean F Jasmin, Isabelle Mercier and Michael P LisantiCirculation. 2007;116:II_13, originally published December 19, 2015
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