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Monocyte chemotactic protein-1 directly induces human vascular smooth muscle proliferation. Am J Physiol Heart Circ Physiol 2002 Oct;283(4):H1455-61

Date

09/18/2002

Pubmed ID

12234797

DOI

10.1152/ajpheart.00188.2002

Scopus ID

2-s2.0-0036784005   71 Citations

Abstract

Although monocyte chemotactic protein-1 (MCP-1) is best known for its ability to recruit mononuclear cells, few studies have examined the effects of this chemokine on other events in the vascular response to injury. The purpose of the present study was to determine the influence of MCP-1 on human vascular smooth muscle (VSMC) proliferation. MCP-1 induced concentration-dependent VSMC proliferation as measured by bromodeoxyuridine (BrdU) uptake. Direct cell counting demonstrated a twofold increase in VSMC after stimulation with MCP-1. This mitogenic effect was similar to that observed with the prototypical atherogenic cytokine platelet-derived growth factor. Immunohistochemistry and Western blot analysis revealed that MCP-1 increased both proliferating nuclear cell antigen and cyclin A expression. Whereas MCP-1 did not promote nuclear factor-kappaB activation, MCP-1-induced VSMC proliferation appeared to be dependent on phosphotidylinositol 3-kinase activation. In conclusion, MCP-1 directly induces VSMC growth, which is associated with activation of cell cycle proteins and intracellular proliferative signals. Within the inflammatory paradigm of vascular remodeling, these data suggest that MCP-1 is more than simply a chemokine but also a potent mitogen for VSMC proliferation.

Author List

Selzman CH, Miller SA, Zimmerman MA, Gamboni-Robertson F, Harken AH, Banerjee A

Author

Michael A. Zimmerman MD, FACS Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aorta, Thoracic
Cell Division
Cells, Cultured
Chemokine CCL2
Cyclin A
Humans
Mitogens
Muscle, Smooth, Vascular
NF-kappa B
Phosphatidylinositol 3-Kinases
Platelet-Derived Growth Factor
Proliferating Cell Nuclear Antigen
Signal Transduction
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0