Dataset Information

17-? Oestradiol prevents cardiovascular dysfunction in post-menopausal metabolic syndrome by affecting SIRT1/AMPK/H3 acetylation.

ABSTRACT:

Background and purpose

Oestrogen therapy is known to induce cardioprotection in post-menopausal metabolic syndrome (PMS). Hence, we investigated the effect of 17-? oestradiol (E2) on functional responses to angiotensin II and cardiovascular dysfunction in a rat model of PMS.

Experimental approach

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.

Key results

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.

Conclusion and implications

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.

SUBMITTER: Bendale DS

PROVIDER: S-EPMC3799593 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

17-β Oestradiol prevents cardiovascular dysfunction in post-menopausal metabolic syndrome by affecting SIRT1/AMPK/H3 acetylation.

Bendale Dhaval Sharad DS Karpe Pinakin Arun PA Chhabra Richa R Shete Sachin Prabhakarrao SP Shah Heta H Tikoo Kulbhushan K

British journal of pharmacology 20131001 4

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>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 transd ...[more]

PMID: 23826814

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