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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: AMP-Activated Protein Kinases, Acetylation, Animals, Aorta, Apoptosis, Cardiomyopathies, Chromatin Assembly and Disassembly, Diet, High-Fat, Disease Models, Animal, Endothelium, Vascular, Enzyme Inhibitors, Estradiol, Estrogen Replacement Therapy, Female, Histones, Insulin Resistance, Metabolic Syndrome, Myocytes, Cardiac, Nitric Oxide Synthase Type III, Ovariectomy, Poly(ADP-ribose) Polymerases, Postmenopause, Rats, Rats, Sprague-Dawley, Receptor, Angiotensin, Type 1, Signal Transduction, Sirtuin 1, Time Factors, Vasoconstriction, Vasodilation, bcl-2-Associated X Protein.
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Does 17-β Oestradiol prevent cardiovascular dysfunction in post-menopausal metabolic syndrome by affecting SIRT1/AMPK/H3 acetylation? Context: Oestrogen therapy is known to induce cardioprotection in post-menopausal metabolic syndrome (PMS). Hence, we investigated the effect of 17-β oestradiol (E2) on functional responses to angiotensin II and cardiovascular dysfunction in a rat model of PMS. PMS was induced in ovariectomized rats by feeding a high-fat diet for 10 weeks. Isometric tension responses of aortic rings to angiotensin II were recorded using an isometric force transducer. TUNEL assay and immunoblotting was performed to assess apoptosis and protein expression respectively in PMS. Endothelial dysfunction in PMS was characterized by enhanced angiotensin II-induced contractile responses and impaired endothelial dependent vasodilatation. This was associated with an increased protein expression of AT1 receptors in the aorta and heart in PMS. PMS induced cardiac apoptosis by activating Bax and PARP protein expression. These changes were associated with a down-regulation in the expression of silent information regulation 2 homologue (SIRT1)/P-AMP-activated PK (AMPK) and increased H3 acetylation in aorta and heart. E2 partially suppressed angiotensin II-induced contractions, restored the protein expression of SIRT1/P-AMPK and suppressed H3 acetylation. The role of SIRT1/AMPK was further highlighted by administration of sirtinol and compound C (ex vivo), which enhanced angiotensin II contractile responses and ablated the protective effect of E2 on PMS.
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Our results provide novel mechanisms for PMS-induced cardiovascular dysfunction involving SIRT1/AMPK/ histone H3 acetylation, which was prevented by E2. The study suggests that therapies targeting SIRT1/AMPK/epigenetic modifications may be beneficial in reducing the risk of cardiovascular disorders. Final Decision: yes