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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Left Ventricle Hypertrophy and Nandrolone ( Decadurabolin )
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<blockquote data-quote="SoCal Guy" data-source="post: 77515" data-attributes="member: 14529"><p><strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/28679058" target="_blank">Pharmacological Inhibition of mTOR Kinase Reverses Right Ventricle Remodeling and Improves Right Ventricle Structure and Function in Rats.</a></strong></p><p><span style="color: #000000"><span style="font-family: 'Arial'">Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased pulmonary artery pressure (PAP), right heart afterload and death. Mechanistic target of </span></span><span style="color: #000000"><span style="font-family: 'Arial'">rapamycin</span></span><span style="color: #000000"><span style="font-family: 'Arial'"> (mTOR) promotes smooth muscle cell proliferation, survival and pulmonary vascular remodeling via two functionally distinct complexes, mTORC1 (supports cell growth) and mTORC2 (promotes cell survival), and dual mTORC1/mTORC2 inhibition selectively induces PAH PAVSMC apoptosis and reverses pulmonary vascular remodeling. The consequences of mTOR inhibition on RV morphology and function are not known. </span></span></p><p><span style="color: #000000"><span style="font-family: 'Arial'"></span></span></p><p><span style="color: #000000"><span style="font-family: 'Arial'">Using SU5416/hypoxia rat model of PH, we report that, in contrast to activation of both, mTORC1 and mTORC2 pathways in small remodeled PAs, RV tissues had predominant up-regulation of mTORC1 signaling accompanied by cardiomyocyte and RV hypertrophy, increased RV wall thickness (RV WT), RV/LV end-diastolic area (EDA) ratio, RV contractility (max dP/dT) and afterload (Ea), and shorter RV acceleration time (RV-AT) compared to controls. Treatment with mTOR kinase inhibitor PP242 at weeks 6-8 post-PH induction suppressed both mTORC1 and mTORC2 in small PAs, but only mTORC1 signaling in RV, preserving basal mTORC2-Akt levels. Vehicle-treated rats showed further PH and RV worsening and profound RV fibrosis. PP242 reversed pulmonary vascular remodeling and prevented neointimal occlusion of small PAs, significantly reduced PAP and pulmonary vascular resistance, reversed cardiomyocyte hypertrophy and RV remodeling, improved max dP/dT, Ea and RV-AT, and prevented development of RV fibrosis. </span></span></p><p><span style="color: #000000"><span style="font-family: 'Arial'"></span></span></p><p><span style="color: #000000"><span style="font-family: 'Arial'">Collectively, this data show predominant role of mTORC1 vs. mTORC2 in RV pathology and suggest potential attractiveness of mTOR inhibition to simultaneously target pulmonary vascular remodeling and RV dysfunction in established PH.</span></span></p></blockquote><p></p>
[QUOTE="SoCal Guy, post: 77515, member: 14529"] [b][URL="https://www.ncbi.nlm.nih.gov/pubmed/28679058"]Pharmacological Inhibition of mTOR Kinase Reverses Right Ventricle Remodeling and Improves Right Ventricle Structure and Function in Rats.[/URL][/b] [COLOR=#000000][FONT=arial]Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased pulmonary artery pressure (PAP), right heart afterload and death. Mechanistic target of [/FONT][/COLOR][COLOR=#000000][FONT=arial]rapamycin[/FONT][/COLOR][COLOR=#000000][FONT=arial] (mTOR) promotes smooth muscle cell proliferation, survival and pulmonary vascular remodeling via two functionally distinct complexes, mTORC1 (supports cell growth) and mTORC2 (promotes cell survival), and dual mTORC1/mTORC2 inhibition selectively induces PAH PAVSMC apoptosis and reverses pulmonary vascular remodeling. The consequences of mTOR inhibition on RV morphology and function are not known. Using SU5416/hypoxia rat model of PH, we report that, in contrast to activation of both, mTORC1 and mTORC2 pathways in small remodeled PAs, RV tissues had predominant up-regulation of mTORC1 signaling accompanied by cardiomyocyte and RV hypertrophy, increased RV wall thickness (RV WT), RV/LV end-diastolic area (EDA) ratio, RV contractility (max dP/dT) and afterload (Ea), and shorter RV acceleration time (RV-AT) compared to controls. Treatment with mTOR kinase inhibitor PP242 at weeks 6-8 post-PH induction suppressed both mTORC1 and mTORC2 in small PAs, but only mTORC1 signaling in RV, preserving basal mTORC2-Akt levels. Vehicle-treated rats showed further PH and RV worsening and profound RV fibrosis. PP242 reversed pulmonary vascular remodeling and prevented neointimal occlusion of small PAs, significantly reduced PAP and pulmonary vascular resistance, reversed cardiomyocyte hypertrophy and RV remodeling, improved max dP/dT, Ea and RV-AT, and prevented development of RV fibrosis. Collectively, this data show predominant role of mTORC1 vs. mTORC2 in RV pathology and suggest potential attractiveness of mTOR inhibition to simultaneously target pulmonary vascular remodeling and RV dysfunction in established PH.[/FONT][/COLOR] [/QUOTE]
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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Left Ventricle Hypertrophy and Nandrolone ( Decadurabolin )
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