Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells

被引:85
作者
Mahadev, Kalyankar [1 ]
Wu, Xiangdong [1 ]
Donnelly, Sylvia [1 ]
Ouedraogo, Raogo [1 ]
Eckhart, Andrea D. [2 ]
Goldstein, Barry J. [1 ]
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Div Endocrinol Diabet & Metab Dis, Dept Med, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Ctr Translat Med,Eugene Feiner Lab Vasc Biol & Th, Philadelphia, PA 19107 USA
关键词
adiponectin; acrp30; VEGF; endothelium; reactive oxygen species; apoptosis; focal adhesions; actin stress fibres; RhoA;
D O I
10.1093/cvr/cvn034
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims Vascular endothelial growth factor (VEGF)-induced endothelial cell migration and angiogenesis are associated with the vascular complications of diabetes mellitus, and adiponectin is an abundant plasma adipokine that exhibits salutary effects on endothelial function. We investigated whether adiponectin suppresses VEGF-induced migration and related signal transduction responses in human coronary artery endothelial cells (HCAECs). Methods and results Using a modified Boyden chamber technique and a monolayer 'wound-healing' assay, both the recombinant adiponectin globular domain and full-length adiponectin protein potently suppressed the migration of HCAEC induced by VEGF. Adiponectin did not increase endothelial. cell apoptosis, as measured by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labelling assay. Adiponectin also suppressed VEGF-induced reactive oxygen species generation, activation of Akt, the mitogen-activated protein kinase ERK and the RhoGTPase RhoA, and induction of the formation of actin stress fibres and focal cellular adhesions. VEGF-stimulated cell migration was inhibited by activation of adenylyl cyclase with forskolin, and adiponectin treatment increased cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) enzymatic activity. Pharmacological inhibition of either adenylyl cyclase or PKA significantly abrogated the effect of adiponectin globular domain to suppress VEGF-induced cell migration. Conclusion Adiponectin suppresses VEGF-stimulated HCAEC migration via cAMP/PKA-dependent signalling, an important effect with implications for a regulatory rote of adiponectin in vascular processes associated with diabetes and atherosclerosis.
引用
收藏
页码:376 / 384
页数:9
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