Journal Article

Regulation of Inflammation-Mediated Endothelial to Mesenchymal Transition with Echinochrome a for Improving Myocardial Dysfunction

Jeong, Seongtae, Han, Jin, Kim, Hojin, Chang, Woochul, Moon, Hanbyeol, Kim, Hyoung, Song, Byeong-Wook, Kim, Jongmin, Vasileva, Elena, Fedoreyev, Sergey, Lee, Min, Mishchenko, Natalia, Stonik, Valentin, Kim, Sejin, Kim, Ran

2022

Overview

Endothelial–mesenchymal transition (EndMT) is a process by which endothelial cells (ECs) transition into mesenchymal cells (e.g., myofibroblasts and smooth muscle cells) and induce fibrosis of cells/tissues, due to ischemic conditions in the heart. Previously, we reported that echinochrome A (EchA) derived from sea urchin shells can modulate cardiovascular disease by promoting anti-inflammatory and antioxidant activity; however, the mechanism underlying these effects was unclear. We investigated the role of EchA in the EndMT process by treating human umbilical vein ECs (HUVECs) with TGF-β2 and IL-1β, and confirmed the regulation of cell migration, inflammatory, oxidative responses and mitochondrial dysfunction. Moreover, we developed an EndMT-induced myocardial infarction (MI) model to investigate the effect of EchA in vivo. After EchA was administered once a day for a total of 3 days, the histological and functional improvement of the myocardium was investigated to confirm the control of the EndMT. We concluded that EchA negatively regulates early or inflammation-related EndMT and reduces the myofibroblast proportion and fibrosis area, meaning that it may be a potential therapy for cardiac regeneration or cardioprotection from scar formation and cardiac fibrosis due to tissue granulation. Our findings encourage the study of marine bioactive compounds for the discovery of new therapeutics for recovering ischemic cardiac injuries.

• Publisher: MDPI AG,MDPI
• Subject: Angiogenesis / antioxidant activity / Bioactive compounds / Biological products / Biosynthesis / cardiac fibrosis / Cardiomyopathy / cardioprotective effect / Cardiovascular diseases / Care and treatment / Carnitine / Cell adhesion & migration / Cell differentiation / Cell migration / cell movement / Cells, Cultured / Chemical properties / echinochrome A / Echinoidea / Endothelial cells / endothelial–mesenchymal transition / Epithelial cells / Epithelial-Mesenchymal Transition / Fibrosis / Granulation / Health aspects / Heart / Heart diseases / histology / Human Umbilical Vein Endothelial Cells / Humans / IL-1β / In vivo methods and tests / Inflammation / Inflammation - drug therapy / Inflammation - pathology / Ischemia / Kinases / Marine invertebrates / Mesenchyme / Migrations / Mitochondria / Mitochondrial DNA / Morphology / Muscles / Myocardial infarction / Myocardium / Organic pigments / Permeability / Phosphorylation / Physiological aspects / Regeneration (biological) / Scars / Sea urchins / Signal Transduction / Smooth muscle / Testing / therapeutics / Umbilical cables / Umbilical vein / umbilical veins