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 beta 1 (TGF-beta 1) 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-beta 1 together stimulated ScR activity 12-fold. In human SMC, EGF and TGF-beta 1, 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-beta 1 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.
Highlights
One characteristic feature of atherosclerotic lesions is the unregulated accumulation of lipoprotein-derived cholesterol and cholesteryl esters in macrophages and smooth muscle cells of the arterial intima
Our previous studies have shown that types I and II scavenger receptors are expressed by rabbit smooth muscle cells and that incubation of the cells with platelet secretory products up-regulates receptor activity [10]
We have shown previously that types I and II scavenger receptor activity in rabbit smooth muscle cells can be up-regulated by phorbol esters, platelet secretory products in serum, and secretion products from activated platelets (10 –12)
Summary
Materials—Heat-inactivated fetal bovine serum was obtained from HyClone Laboratories (Logan, UT). Dulbecco’s modified Eagle’s medium, Dulbecco’s phosphate-buffered saline, penicillin, and streptomycin were obtained from Life Technologies, Inc. Two human aortic smooth muscle cell lines and growth medium with (SmGM 2) or without (SmBM) serum were purchased from Clonetics (San Diego). The cells were washed three times with SmBM or Dulbecco’s modified Eagle’s medium, incubated with DiI-labeled acetyl-LDL (AcLDL) (5 g/ml) for 8 h at 37 °C, and processed for fluorescence-activated cell sorter (FACS) analysis as described [10]. The concentrations of anti-PDGF and anti-TGF-1 antibodies used were sufficient to block the effect of recombinant PDGF BB (50 ng/ml) and TGF-1 (20 ng/ml) on scavenger receptor activity in rabbit smooth muscle cells, respectively. The concentrations of antiIGF-I and anti-EGF antibodies used were sufficient to block the effect of IGF-I (20 ng/ml) and EGF (10 ng/ml) on smooth muscle cell proliferation measured by assaying the mitochondrial dehydrogenase activity as described (Boehringer Mannheim)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
