Journal
VASCULAR PHARMACOLOGY
Volume 145, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2022.107086
Keywords
Soluble epoxide hydrolase; Atherosclerosis; Vascular smooth muscle cell; Phenotypic switching; N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl]-urea
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Funding
- Main Research Program of the KoreaFood Research Institute - Ministry of Science, ICT, and Future Planning [E0210102-02]
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Atherosclerosis is a chronic inflammation caused by interactions between circulating factors and various cell types in blood vessel walls. This study found that TPPU has anti-atherosclerotic effects, potentially by suppressing the phenotype switching of VSMCs.
Atherosclerosis manifests as a chronic inflammation resulting from multiple interactions between circulating factors and various cell types in blood vessel walls. Growing evidence shows that phenotypic switching and proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the progression of athero-sclerosis. Soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids are mediated by vascular inflammation. N-[1-(1-oxopropyl)-4-piperidinyl]-N & PRIME;-[4-(trifluoromethoxy)phenyl]-urea (TPPU) is an sEH inhibitor. This study investigated the therapeutic effect of TPPU on atherosclerosis in vivo and homocysteine-induced vascular inflammation in vitro and explored their molecular mechanisms. We found that TPPU decreased WD-induced atherosclerotic plaque lesions, inflammation, expression of sEH, and nicotinamide adenine dinucleotide phos-phate oxidase-4 (Nox4), and increased the expression of contractile phenotype marker of aortas in ApoE (-/-) mice. TPPU also inhibited homocysteine-stimulated VSMC proliferation, migration, and phenotypic switching, and reduced Nox4 in human-aorta-VSMC regulation. We conclude that TPPU has anti-atherosclerotic effects, potentially because of the suppression of VSMC phenotype switching. Thus, TPPU could be a potential thera-peutic target for phenotypic switching attenuation in atherosclerosis.
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