title: Sparstolonin B suppresses rat vascular smooth muscle cell proliferation, migration, inflammatory response and lipid accumulation.
abstract: Vascular smooth muscle cells (VSMCs) play a crucial role in atherosclerotic lesion formation. Sparstolonin B (SsnB) is a TLR2/TLR4 antagonist that inhibits inflammatory responses in multiple cell types. Herein, we investigated if SsnB inhibited VSMC proliferation, migration, inflammatory response and lipid accumulation. We found that SsnB suppressed VSMC proliferation and migration induced by PDGF. SsnB significantly suppressed the expression of MCP-1, TNFα and IL-6 in VSMCs stimulated by either lipopolysaccharide (LPS) or PDGF. Erk1/2 and Akt signaling pathways, which are responsible for the VSMC inflammatory response, were activated by LPS or PDGF stimulation, and SsnB significantly inhibited their activation. SsnB also substantially suppressed the intracellular cholesterol accumulation in VSMCs loaded with acetylated LDL. Mechanistically, SsnB remarkably repressed LPS-induced up-regulation of CD36, which is responsible for lipid uptake, and dramatically reversed LPS-induced inhibition of ABCA1, which promotes the efflux of intracellular free cholesterol. In conclusion, our results indicate that SsnB significantly inhibits VSMC proliferation, migration, inflammatory responses and lipid accumulation. Along with the previously reported anti-inflammatory activities of SsnB on macrophages and vascular endothelial cells, our data strongly suggest that SsnB may be developed as a new anti-atherogenic therapy.
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, United States; Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors: Qing
authors: Q
authors: Liu
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
authors: Jianping
authors: J
authors: Li
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Qiaoli
authors: Q
authors: Liang
authors: Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors: Dawei
authors: D
authors: Wang
authors: Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors: Yi
authors: Y
authors: Luo
authors: Department of Nutrition and Food Hygiene, Fourth Military Medical University, Xi'an 710032, China.
authors: Fang
authors: F
authors: Yu
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
authors: Joseph S
authors: JS
authors: Janicki
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, United States. Electronic address: daping.fan@uscmed.sc.edu.
authors: Daping
authors: D
authors: Fan
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008055:Lipids / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D018836:Inflammation Mediators; D008055:Lipids; C561322:sparstolonin B
keywords: Atherogenesis; Inflammation; Lipid accumulation; Sparstolonin B; VSMC