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Research Paper|Volume 14, Issue 2|pp 800—810

The interaction protein of SORBS2 in myocardial tissue to find out the pathogenic mechanism of LVNC disease

Chunyan Li1, Yang Zheng3, Ying Liu1, Guo Hong Jin1, Haizhou Pan4, Fenghui Yin5, Jun Wu1,2
  • 1Department of Clinical Laboratory, Beijing Jishuitan Hospital, Beijing 100035, China
  • 2Department of Laboratory Medicine, Peking University Fourth School of Clinical Medicine, Beijing Jishuitan Hospital, Xicheng, Beijing 100035, China
  • 3Department of Orthopaedics, Fourth Medical Center of PLA General Hospital, People's Republic of China, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Beijing 10048, China
  • 4Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou 310014, China
  • 5The Third People’s Hospital of Chengdu, Chengdu 610031, China
* Equal contribution
Received: August 28, 2021Accepted: December 8, 2021Published: January 20, 2022
https://doi.org/10.18632/aging.203841

Copyright: © 2022 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Left ventricular noncompaction cardiomyopathy (LVNC) is a cardiac disorder characterized by an excessive trabecular meshwork of deep intertrabecular recesses within the ventricular myocardium. Sorbin and SH3 domain-containing protein 2 (SORBS2) converges on the actin and microtubule cytoskeleton. Here, we investigated the proteins interacting with SORBS2 to elucidate the pathogenic mechanism of LVNC. As reported in previous studies, SORBS2 enhances the occurrence of LVNC by potentiating heart failure, but the specific mechanism remains unclear.

Methods: Building from our previous finding of elevated SORBS2 levels in LVNC hearts, we screened for proteins interacting with SORBS2 by proteomics and conducting IP experiments. Co-IP and immunofluorescence were used to verify the effects.

Results: We selected several proteins with high scores and high coverage that could be closely related to SORBS2 according to earlier reports showing a correlation with LVNC for verification. We finally obtained several proteins that were related to the pathogenesis of LVNC and also interacted with SORBS2, such as α-actinin, β-tubulin, MYH7, FLNA, MYBPC3, YWHAQ and DES, and YWHAQ was the most associated.

Conclusions: We focused on the YWHAQ protein, and we identified a novel mechanism through which SORBS2 interacts with YWHAQ, having a negative effect on the cell cycle, potentially leading to LVNC.