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    Metformin improves heart failure

    yoly
    yoly
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    Metformin improves heart failure Empty Metformin improves heart failure

    Post by yoly on Fri Dec 21 2018, 11:36

    (Complete study on link)
    Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance

    http://jgp.rupress.org/content/early/2018/12/19/jgp.201812259

    Abstract

    Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by a preserved ejection fraction but increased diastolic stiffness and abnormalities of filling. Although the prevalence of HFpEF is high and continues to rise, no effective therapies exist; however, the diabetic drug metformin has been associated with improved diastolic function in diabetic patients. Here we determine the therapeutic potential of metformin for improving diastolic function in a mouse model with HFpEF-like symptoms. We combine transverse aortic constriction (TAC) surgery with deoxycorticosterone acetate (DOCA) supplementation to obtain a mouse model with increased diastolic stiffness and exercise intolerance. Echocardiography and pressure–volume analysis reveal that providing metformin to TAC/DOCA mice improves diastolic function in the left ventricular (LV) chamber. Muscle mechanics show that metformin lowers passive stiffness of the LV wall muscle. Concomitant with this improvement in diastolic function, metformin-treated TAC/DOCA mice also demonstrate preserved exercise capacity. No metformin effects are seen in sham operated mice. Extraction experiments on skinned ventricular muscle strips show that the metformin-induced reduction of passive stiffness in TAC/DOCA mice is due to an increase in titin compliance. Using phospho-site-specific antibodies, we assay the phosphorylation of titin’s PEVK and N2B spring elements. Metformin-treated mice have unaltered PEVK phosphorylation but increased phosphorylation of PKA sites in the N2B element, a change which has previously been shown to lower titin’s stiffness. Consistent with this result, experiments with a mouse model deficient in the N2B element reveal that the beneficial effect of metformin on LV chamber and muscle stiffness requires the presence of the N2B element. We conclude that metformin offers therapeutic benefit during HFpEF by lowering titin-based passive stiffness.
    Jan1
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    Metformin improves heart failure Empty Re: Metformin improves heart failure

    Post by Jan1 on Sat Dec 22 2018, 13:09

    Many thanks for this Yoly, and including the link to the full paper.

    I'm no scientific expert, but I think metformin may have possible advantages, and it will be interesting to see further studies done that are required that focus specifically on the diastolic effect of metformin in HFpEF patients.

    All the best Jan

      Current date/time is Mon May 20 2019, 00:14