Modulation of P2Y6R expression exacerbates pressure overload-induced cardiac remodeling in mice

DOI PDF Web Site 5 Citations 45 References Open Access

Description

<jats:title>Abstract</jats:title><jats:p>Cardiac tissue remodeling caused by hemodynamic overload is a major clinical outcome of heart failure. Uridine-responsive purinergic P2Y<jats:sub>6</jats:sub> receptor (P2Y<jats:sub>6</jats:sub>R) contributes to the progression of cardiovascular remodeling in rodents, but it is not known whether inhibition of P2Y<jats:sub>6</jats:sub>R prevents or promotes heart failure. We demonstrate that inhibition of P2Y<jats:sub>6</jats:sub>R promotes pressure overload-induced sudden death and heart failure in mice. In neonatal cardiomyocytes, knockdown of P2Y<jats:sub>6</jats:sub>R significantly attenuated hypertrophic growth and cell death caused by hypotonic stimulation, indicating the involvement of P2Y<jats:sub>6</jats:sub>R in mechanical stress-induced myocardial dysfunction. Unexpectedly, compared with wild-type mice, deletion of P2Y<jats:sub>6</jats:sub>R promoted pressure overload-induced sudden death, as well as cardiac remodeling and dysfunction. Mice with cardiomyocyte-specific overexpression of P2Y<jats:sub>6</jats:sub>R also exhibited cardiac dysfunction and severe fibrosis. In contrast, P2Y<jats:sub>6</jats:sub>R deletion had little impact on oxidative stress-mediated cardiac dysfunction induced by doxorubicin treatment. These findings provide overwhelming evidence that systemic inhibition of P2Y<jats:sub>6</jats:sub>R exacerbates pressure overload-induced heart failure in mice, although P2Y<jats:sub>6</jats:sub>R in cardiomyocytes contributes to the progression of cardiac fibrosis.</jats:p>

Journal

  • Scientific Reports

    Scientific Reports 10 (1), 13926-, 2020-08-18

    Springer Science and Business Media LLC

Citations (5)*help

See more

References(45)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top