Synergistic Effects of Growth Factors on the Regulation of Smooth Muscle Cell Scavenger Receptor Activity

doi:10.1074/jbc.270.37.21672

Synergistic Effects of Growth Factors on the Regulation of Smooth Muscle Cell Scavenger Receptor Activity (*)

From the Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, Department of Pathology, University of California, San Francisco, California 94141-9100

^§To whom correspondence should be addressed:
Gladstone Institute of Cardiovascular Disease, P. O. Box 419100, San Francisco, CA 94141-9100.
Tel.: 415-826-7500; Fax: 415-285-5632.

Abstract

Rabbit smooth muscle cells (SMC) express types I and II scavenger receptors (ScR) that are up-regulated by platelet secretion products. In the current studies we investigated the effect of growth factors secreted by platelets on ScR activity in rabbit and human SMC. Platelet-derived growth factor (PDGF BB) and transforming growth factor β (TGF-β) at 10 ng/ml increased ScR activity in rabbit SMC (by approximately 4- and 2-fold, respectively) but not in human SMC. Epidermal growth factor (EGF) or insulin-like growth factor I (IGF-I) alone had little effect on SMC ScR activity. The growth factors had synergistic effects on ScR activity and on types I and II ScR mRNA expression. In rabbit SMC, PDGF BB, EGF, and TGF-β together stimulated ScR activity 12-fold. In human SMC, EGF and TGF-β, together with either IGF-I or PDGF BB, stimulated receptor activity approximately 7-fold. Growth factor-mediated induction of ScR activity in rabbit and human SMC was blocked by the tyrosine kinase inhibitor tyrphostin 47, whereas the induction of ScR activity in rabbit but not human SMC was blocked by the protein kinase C inhibitor MDL.29,152. Studies using neutralizing antibodies demonstrated that TGF-β is the predominant factor in in vitro preparations of platelet secretory products which regulates ScR activity. The growth factors that act synergistically in regulating ScR activity in vitro are all present in atherosclerotic lesions, where they are produced by macrophages, endothelial cells, SMC, and platelets. The data suggest that these growth factors may regulate ScR activity in SMC in vivo and contribute to foam cell formation.

Footnotes

↵* This work was supported in part by National Institutes of Health Program Project Grant HL47660. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

PDGF

platelet-derived growth factor

EGF

epidermal growth factor

IGF-I

insulin-like growth factor I

TGF-β

transforming growth factor β

DiI

1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate

LDL

low density lipoproteins

Ac-LDL

acetyl low density lipoproteins

FACS

fluorescence-activated cell sorter

TNF-α

tumor necrosis factor α

IFN-

interferon .
- Received May 26, 1995.
- Revision received July 3, 1995.