Novel phytopeptide osmotin mimics preventive effects of adiponectin on vascular inflammation and atherosclerosis

Abstract

Introduction: The novel phytohormone, osmotin, has been reported to act like mammalian adiponectin through PHO36/AdipoR1 in various in vitro and in vivo models. However, there have been no reports regarding the precise effects of osmotin on atherosclerosis.

Methods: We assessed the atheroprotective effects of osmotin on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), human leukemic monocyte (THP-1) adhesion, inflammatory responses, and foam cell formation in THP-1-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs). We examined whether 4-week infusion of osmotin could suppress the development of aortic atherosclerotic lesions in apolipoprotein E-deficient (ApoE^-/-) mice.

Results: AdipoR1 was abundantly expressed in HUVECs, HASMCs, THP-1, and derived macrophages. Osmotin suppressed lipopolysaccharide-induced upregulation of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in HUVECs, and TNF-α-induced THP-1-HUVEC adhesion. In THP-1-derived macrophages, osmotin suppressed the inflammatory M1 phenotype, lipopolysaccharide-induced secretion of interleukin-6 and TNF-α, and oxidized low-density lipoprotein-induced foam cell formation associated with CD36 and acyl-CoA:cholesterol acyltransferase 1 downregulation and ATP-binding cassette transporter A1 upregulation. In HASMCs, osmotin suppressed angiotensin II-induced migration, proliferation, collagen-1 and fibronectin expression, and matrix metalloproteinase-2 activity without inducing apoptosis. Infusion of osmotin into ApoE^-/- mice prevented the development of aortic atherosclerotic lesions with reductions of intraplaque pentraxin-3 expression, fasting plasma glucose, and insulin resistance.

Conclusions: This study provided the first evidence that osmotin exerts preventive effects on vascular inflammation and atherosclerosis, which may facilitate the development of new therapeutic modalities for combating atherosclerosis and related diseases.

Keywords: Atherosclerosis; Endothelial cell; Inflammation; Macrophage; Osmotin; Vascular smooth muscle cell.