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05.01.2021: Publication Alert - Elevated myocardial SORBS2 and the underlying implications in leftventricular noncompaction cardiomyopathy

Elevated myocardial SORBS2 and the underlying implications in leftventricular noncompaction cardiomyopathy

Abstract

Left ventricular noncompaction cardiomyopathy (LVNC) is a hereditary heart disease characterized by an excessive trabecular meshwork of deep intertrabecular recesses within the ventricular myocar-dium. The guidelines for management of LVNC patients aim to improve quality of life by preventing cardiacheart failure. However, the mechanism underlying LVNC-associated heart failure remains poorly understood.
Methods: Using protein mass spectrometry analysis, we established that Sorbin And SH3 Domain Containing 2 (SORBS2) is up-regulated in LVNC hearts without changes to structure proteins. We conductedin vivoexperiments wherein the heart tissues of wild-type mice were injected with an AAV9 vector to overexpress SORBS2, followed by analysis using echocardiography, T-tubule analysis and Ca2+ imaging to identify func-tional and morphological changes. In addition, we analyzed the function and structure of SORBS2 overex-pressing human embryonic stem cell (hESC) derived cardiomyocytes (hESC-CM) via immunoblotting, immunohistochemistry, immunofluorescence, and confocal Ca2+ imaging.

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