2020 - Elevated myocardial SORBS2 and the underlying implications in leftventricular noncompaction cardiomyopathy
CardioExcyte 96 publication in EBioMedicine (2020)
Li C., Liu F., Liu S., Pan H., Du H., Huang J., Xie Y., Li Y., Zhao R., Wei Y.
EBioMedicine (2020) doi: 10.1016/j.ebiom.2020.102695
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.