LTBP2 Knockdown Ameliorates Cardiac Fibrosis and Apoptosis via Attenuating NF-κB Signaling Pathway and Oxidative Stress in Mice with Cardiac Hypertrophy

Abstract

At present, there is no therapeutic approach available to reverse the progression of pathological fibrosis and ventricle chamber stiffening. This study is designed to explore the effects of latent transforming growth factor-beta-binding protein 2 (LTBP2) on cardiac fibrosis in hypertrophic cardiomyopathy and the underlying mechanisms. The key differential gene LTBP2 is identified by mRNA sequencing. Ang II-induced cells and mice are treated with LTBP2 si-RNA or knockdown adenovirus, respectively, and the indicators of cardiac function, oxidative stress, cardiac fibrosis, apoptosis, and remodeling are examined. The underlying mechanism is elucidated in vitro by oxidative stress and an agonist of nuclear factor-kappa B (NF-κB). LTBP2 is upregulated in the cardiac tissue of mice with Ang II-mediated HF. The knockdown of LTBP2 enhanced cardiac function, attenuated cardiac fibrosis, apoptosis, hypertrophy, and oxidative stress injury, and suppressed NF-κB expression. These results are validated in vitro. The effects of LTBP2 gene silencing are reversed by either NF-κB or oxidative stress agonists in vitro. Taken together, these findings suggest that LTBP2 knockdown alleviates HF by inhibiting cardiac fibrosis, apoptosis, and hypertrophy via attenuating NF-κB signaling pathway and oxidative stress. Thus, targeting LTBP2 may be a novel approach to the treatment of HF.