Localization of PDGF-B Protein in Macrophages in All Phases of Atherogenesis

Abstract

Lesions of atherosclerosis occur in the innermost layer of the artery wall and consist primarily of proliferated smooth muscle cells surrounded by large amounts of connective tissue, numerous lipid-laden macrophages, and varying numbers of lymphocytes. Growth-regulatory molecules may be involved in intimal accumulation and proliferation of smooth muscle cells responsible for the occlusive lesions of atherosclerosis. Platelet-derived growth factor (PDGF) B-chain protein was found within macrophages in all stages of lesion development in both human and nonhuman primate atherosclerosis. Thus macrophages may play a critical role in the disease by providing PDGF, a potent chemotactic and growth-stimulatory molecule, to the intimal smooth muscle cells.

Atherosclerosis-related molecular alteration of the human Ca V 1.2 calcium channel α 1C subunit

“…This association is consistent with and supported by earlier observations that in normal human fibroblasts, serum deprivation induced an increase, whereas mitogens (basic fibroblast growth factor, EGF, and insulin), second messengers (cAMP and Ca 2ϩ ) or cell-cell contact inhibition caused strong reduction in the expression of the L-type Ca 2ϩ channels (9). PDGF-BB is a mitogenic factor known to be a stimulus for neointimal proliferation and migration of VSMC in atherosclerosis (36,37). Here we have shown increased expression of both PDGF-BB and its receptor in VSMC D .…”

NGF Activates Similar Intracellular Signaling Pathways in Vascular Smooth Muscle Cells as PDGF-BB But Elicits Different Biological Responses

“…Growth factors, such as platelet-derived growth factor (PDGF) and insulin-like growth factor 1 (IGF-1), and their receptors show increased expression in the arterial wall after balloon angioplasty. [2][3][4][5][6] However, the biological responses elicited by these 2 agonists are different in that PDGF mediates both smooth muscle cell proliferation and migration whereas IGF-1 specifically induces only smooth muscle cell migration. 7 Ligand binding to the PDGF and IGF-1 receptor tyrosine kinases induces autophosphorylation of tyrosines within the cytoplasmic domain of the receptors, resulting in the recruitment and activation of specific signaling molecules that may mediate the migration and proliferation of vascular smooth muscle cells in response to vascular injury.…”

Local Delivery of Heparin Inhibits Neointimal Hyperplasia in Injured Rabbit Artery.

“…[4][5][6][7]9) These interactions between blood and the vessel wall promote smooth muscle cell migration and proliferation. Thrombogenicity of the vascular surface after balloon injury is considered to be an important factor in restenosis.…”