Induction of endothelial cell proliferation by angiogenic factors released by activated monocytes.
BACKGROUND
Cell-cell interaction is an essential component of atherosclerotic plaque development. Activated monocytes appear to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the production of various growth factors that induce proliferation of different cell types that are involved in the plaque development. Using serum free co-culture method, we determined the effect of monocytes on endothelial cell proliferation.


METHODS
Endothelial cell proliferation is determined by the amount of [3H]thymidine incorporated in to the DNA. Basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in the conditioned medium were determined by ELISA.


RESULTS
Conditioned medium from unactivated monocytes partially inhibited endothelial cell proliferation, whereas conditioned medium from activated monocytes promoted endothelial cell proliferation. The mitogenic effect of conditioned medium derived from activated monocytes is due to the presence of b-FGF, VEGF and IL-8. Neutralizing antibodies against b-FGF, VEGF and IL-8 partially reversed the mitogenic effect of conditioned medium derived from activated monocytes. When b-FGF, VEGF and IL-8 were immunoprecipitated from conditioned medium derived from activated monocytes, it is less mitogenic to endothelial cells.


CONCLUSIONS
Activated monocytes may play an important role in the development of atherosclerotic plaque by producing endothelial cell growth factors.
Pakala
Rajbabu
R
Division of Cardiology, Department of Internal Medicine, The University of Texas-Houston, Houston, TX, USA. rajbabu.pakala@medstar.net
Watanabe
Takuya
T
Benedict
Claude R
CR
D043925:Angiogenesis Inducing Agents / Q000032:analysis / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology*; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D016895:Culture Media, Serum-Free / Q000737:chemistry / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D013936:Thymidine / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016895:Culture Media, Serum-Free; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013936:Thymidine