BACKGROUND: Hyperlipidemia inhibits proliferation of endothelial cells (ECs) in culture and angiogenesis in vivo and in arterial explants. Elucidation of the mechanisms may suggest novel therapies against atherosclerosis. METHODS AND RESULTS: Basic fibroblast growth factor (bFGF) expression and mitogenic effects were assessed in bovine aortic ECs incubated with oxidized LDL (ox-LDL). Compared with native LDL and lipoprotein-free controls, ox-LDL reduced bFGF mRNA levels in a time- and concentration-dependent manner, 100 microg/mL producing a maximum reduction of 40% to 50% within 24 to 48 hours. There were commensurate reductions in intracellular and extracellular bFGF concentrations, DNA and total RNA syntheses, and cell replication. FGF receptor 1 and beta-actin mRNA levels were unchanged. Ox-LDL accelerated bFGF mRNA degradation in actinomycin D-treated cells. However, inhibition of bFGF expression by ox-LDL was attenuated by cyclohexamide, indicating a requirement for continuous new protein synthesis for posttranscriptional destabilization. Reduced syntheses of DNA and total RNA were completely restored by bFGF but not by vascular endothelial growth factor. Inhibition of total RNA synthesis achieved by exposing cells to a bFGF-neutralizing antibody was similar in magnitude to that induced by ox-LDL. CONCLUSIONS: Cytotoxic effects of ox-LDL on ECs are attributable in part to suppression of bFGF expression.
BACKGROUND:Hyperlipidemia inhibits proliferation of endothelial cells (ECs) in culture and angiogenesis in vivo and in arterial explants. Elucidation of the mechanisms may suggest novel therapies against atherosclerosis. METHODS AND RESULTS:Basic fibroblast growth factor (bFGF) expression and mitogenic effects were assessed in bovine aortic ECs incubated with oxidized LDL (ox-LDL). Compared with native LDL and lipoprotein-free controls, ox-LDL reduced bFGF mRNA levels in a time- and concentration-dependent manner, 100 microg/mL producing a maximum reduction of 40% to 50% within 24 to 48 hours. There were commensurate reductions in intracellular and extracellular bFGF concentrations, DNA and total RNA syntheses, and cell replication. FGF receptor 1 and beta-actin mRNA levels were unchanged. Ox-LDL accelerated bFGF mRNA degradation in actinomycin D-treated cells. However, inhibition of bFGF expression by ox-LDL was attenuated by cyclohexamide, indicating a requirement for continuous new protein synthesis for posttranscriptional destabilization. Reduced syntheses of DNA and total RNA were completely restored by bFGF but not by vascular endothelial growth factor. Inhibition of total RNA synthesis achieved by exposing cells to a bFGF-neutralizing antibody was similar in magnitude to that induced by ox-LDL. CONCLUSIONS:Cytotoxic effects of ox-LDL on ECs are attributable in part to suppression of bFGF expression.
Authors: Jahaira Lopez-Pastrana; Lucas M Ferrer; Ya-Feng Li; Xinyu Xiong; Hang Xi; Ramon Cueto; Jun Nelson; Xiaojin Sha; Xinyuan Li; Ann L Cannella; Princess I Imoukhuede; Xuebin Qin; Eric T Choi; Hong Wang; Xiao-Feng Yang Journal: J Biol Chem Date: 2015-06-02 Impact factor: 5.157
Authors: Andreas Schober; Maliheh Nazari-Jahantigh; Yuanyuan Wei; Kiril Bidzhekov; Felix Gremse; Jochen Grommes; Remco T A Megens; Kathrin Heyll; Heidi Noels; Michael Hristov; Shusheng Wang; Fabian Kiessling; Eric N Olson; Christian Weber Journal: Nat Med Date: 2014-03-02 Impact factor: 53.440
Authors: David F Schaeffer; Maziar Riazy; Kuljit S Parhar; Johnny H Chen; Vincent Duronio; Tatsuya Sawamura; Urs P Steinbrecher Journal: J Lipid Res Date: 2009-04-09 Impact factor: 5.922