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2020 - Elevated myocardial SORBS2 and the underlying implications in leftventricular noncompaction cardiomyopathy

Icon CE   CardioExcyte 96 publication in EBioMedicine (2020)

Authors:
Li C., Liu F., Liu S., Pan H., Du H., Huang J., Xie Y., Li Y., Zhao R., Wei Y.

Journal:
EBioMedicine (2020) doi: 10.1016/j.ebiom.2020.102695


Abstract:

Left ventricular noncompaction cardiomyopathy (LVNC) is a hereditary heart disease character-ized 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 Containing2 (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 overexpressSORBS2, 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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