caa a22 4500 606235760 CHVBK 20210128101244.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2540-x doi (NATIONALLICENCE)springer-10.1007/s11010-015-2540-x Dyslipidemia regulates thrombospondin-1-induced vascular smooth muscle cell chemotaxis [Elektronische Daten] [Pratik Desai, Jeffrey Stein, Sufyan Siddiqui, Kristopher Maier, Vivian Gahtan] Dyslipidemia is a risk factor for intimal hyperplasia (IH). Key to IH is vascular smooth muscle cell (VSMC) migration. Thrombospondin-1 (TSP-1) is a matricellular protein that stimulates VSMC migration. Hypothesis: HDL will inhibit and LDL will augment TSP-1-induced VSMC chemotaxis. VSMC chemotaxis will be inhibited by the HDL moiety, S1P, through the S1PR1 receptor, and augmented by the LDL component, LPA, through the LPAR1 receptor. The goal of this study was to determine the effect of HDL and LDL and their receptors on TSP-1-induced VSMC chemotaxis. For VSMC chemotaxis to TSP-1 cells received the following pretreatments: low (25µg/ml) or optimal (75µg/ml) concentration of HDL, S1P, optimal (75µg/ml) or high (175µg/ml) concentration of LDL, or LPA. For the receptor studies, VSMCs were transfected with siRNA to S1PR1, S1PR3, LPAR1, LPAR2, LPAR3, or a S1PR2 receptor antagonist. The TSP-1-induced chemotaxis results were (1) HDL (25µg/ml) or LDL (75µg/ml) exhibited no effect on chemotaxis; (2) HDL (75µg/ml) inhibited chemotaxis by 50.9±8% and S1P by 43.4±11.6%; (3) LDL (175µg/ml) augmented chemotaxis by 30±10.4% and LPA by 25.6±12.3%; (4) S1PR1 and S1PR3 knockdown and S1PR2 antagonist-treated cells augmented chemotaxis; and (5) LPAR1 and LPAR2 knockdown inhibited and LPAR3 knockdown had no effect on chemotaxis. In conclusion, HDL/S1P inhibits, while LDL/LPA stimulates TSP-1-induced VSMC chemotaxis. The HDL/S1P effect is mediated by the S1PR1-3 receptors. The LDL/LPA effects are mediated by the LPAR1 and LPAR2 receptors, but not LPAR3. Therefore, lipids have significant effects on TSP-1-induced VSMC chemotaxis. Springer Science+Business Media New York (outside the USA), 2015 Thrombospondin-1 nationallicence Muscle nationallicence Smooth nationallicence Chemotaxis nationallicence Dyslipidemia nationallicence Lipoproteins nationallicence Desai Pratik Department of Veterans Affairs Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA aut Stein Jeffrey Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut Siddiqui Sufyan Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut Maier Kristopher Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut Gahtan Vivian Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 85-91 0300-8177 410:1-2<85 2015 410 11010 https://doi.org/10.1007/s11010-015-2540-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2540-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Desai Pratik Department of Veterans Affairs Healthcare Network Upstate New York at Syracuse, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Stein Jeffrey Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Siddiqui Sufyan Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Maier Kristopher Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Gahtan Vivian Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, 13206, Syracuse, NY, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 85-91 0300-8177 410:1-2<85 2015 410 11010