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• W2155486245 abstract "Background— Caveolins (Cavs), the principal structural proteins of caveolar microdomains, have been implicated in the development of pulmonary hypertension (PH). Mice with homozygous deletion of the Cav-1 gene develop PH and right ventricular hypertrophy (RVH). Reductions in pulmonary Cav-1 expression have been shown in several animal models of PH and in patients with severe PH. Whether in vivo modulation of Cav-1 expression could affect the development of PH and RVH remains unknown. Therefore, we investigated the effect of in vivo administration of a Cav-1 mimetic peptide on the development of monocrotaline (MCT)-induced PH. Methods and Results— Thirty minutes after injection of saline or 60 mg/kg MCT, rats were assigned to receive a daily injection of saline, a peptide corresponding to the homeodomain of the Drosophila transcription factor antennapedia (AP; 2.5 mg · kg −1 · d −1 ), or a peptide consisting of the Cav-1–scaffolding domain coupled to AP (AP-Cav; 2.5 mg · kg −1 · d −1 ) for 2 weeks. MCT and MCT+AP rats developed PH with respective right ventricular systolic pressures of 40.2±1.5 and 39.6±1.5 mm Hg. Administration of AP-Cav to MCT rats significantly reduced the right ventricular systolic pressure to 30.1±1.3 mm Hg. MCT and MCT+AP rats also developed pulmonary artery medial hypertrophy and RVH, which was normalized by administration of AP-Cav. Mechanistically, the development of PH was associated with reduced expression of pulmonary Cav-1 and Cav-2, hyperactivation of the STAT3 signaling cascade, and upregulation of cyclin D1 and D3 protein levels, all of which were prevented by administration of AP-Cav. Conclusions— Short-term administration of a Cav-based cell-permeable peptide to MCT rats prevents the development of pulmonary artery medial hypertrophy, PH, and RVH." @default.
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• W2155486245 date "2006-08-29" @default.
• W2155486245 modified "2023-10-15" @default.
• W2155486245 title "Short-Term Administration of a Cell-Permeable Caveolin-1 Peptide Prevents the Development of Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy" @default.
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• W2155486245 doi "https://doi.org/10.1161/circulationaha.106.634709" @default.
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