Adropin inhibits the progression of atherosclerosis in ApoE^-/-/Enho^-/- mice by regulating endothelial-to-mesenchymal transition.

ABSTRACT: Adropin, a secreted protein, coded by energy homeostasis-associated gene (Enho), is recently reported to modulate atherogenesis, with endothelial-to-mesenchymal transition (EndMT) involved in the early process. We explored whether adropin may alleviate atherosclerosis by regulating EndMT. We found that an intraperitoneal injection of adropin [105 μg/(kg·d) for 13 weeks] inhibited the progression of high-fat diet (HFD)-induced aortic atherosclerosis in apolipoprotein E-deficient mice (ApoE^-/-) and those with double gene deletion (ApoE^-/-/Enho^-/-), as detected by Oil Red O and haematoxylin-eosin staining. In the aortas of ApoE^-/- mouse, adropin treatment ameliorated the decrease in the mRNA expression of endothelial cell markers (leukocyte differentiation antigen 31, CD31, and vascular endothelial cadherin, VE-cadherin), but increased that of EndMT markers (alpha smooth muscle actin, α-SMA, and fibroblasts specific protein-1). In vitro, an adropin treatment (30 ng/ml) arrested the hydrogen peroxide (H₂O₂)-induced EndMT in human umbilical vein endothelial cells (HUVECs), attenuated the morphological changes of HUVECs, reduced the number of immunofluorescence-positive α-SMA, increased the mRNA and protein expressions of CD31 and VE-cadherin, and decreased those of α-SMA. Furthermore, the adropin treatment decreased the mRNA and protein expressions of transforming growth factor (TGF)-β1 and TGF-β2, and suppressed the phosphorylation of downstream signal protein Smad2/3 in HUVECs. These mitigative effects of adropin on H₂O₂-induced EndMT were reversed by the transfection of TGF-β plasmid. The findings signify that adropin treatment may alleviate the atherosclerosis in ApoE^-/-/Enho^-/- mice by inhibiting EndMT via the TGF-β/Smad2/3 signaling pathway.

SUBMITTER: Ying T 

PROVIDER: S-EPMC10616072 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature