Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques.

Abstract

How an atherosclerotic plaque evolves from minimal diffuse intimal hyperplasia to a critical lesion is not well understood. Cellular proliferation is a relatively infrequent and modest event in both primary and restenotic coronary atherectomy specimens, leading us to believe that other processes, such as the formation of extracellular matrix, cell migration, neovascularization, and calcification might be more important for lesion formation. The investigation of proteins that are overexpressed in plaque compared with the normal vessel wall may provide clues that will help determine which of these processes are key to lesion pathogenesis. One such molecule, osteopontin (OPN), is an arginine-glycine-aspartate-containing acidic phosphoprotein recently shown to be a novel component of human atherosclerotic plaques and selectively expressed in the rat neointima following balloon angioplasty. Using in situ hybridization and immunohistochemical I dentifying the processes and molecular mediators of atherosclerotic plaque formation are currently areas of intense investigation. While focal smooth muscle cell (SMC) accumulations have been considered a hallmark of atherosclerosis and restenosis, 15 recent data suggest that the frequency of SMC replication in plaques is low. 6 -7 Thus, smooth muscle proliferation may not be a dominant event in lesion progression. Instead, other processes, such as cell migration, extracellular matrix formation, neovascularization, and calcification may be important pathophysiological events that are possibly linked to the expression of genes unique to atherosclerotic plaque and not found in the normal vessel wall. Examples of molecules that are overexpressed in the plaque compared with the normal vessel wall include platelet-derived growth factor-A, 8 bone morphogenetic protein-2a, 9 the major histocompatibility complex class II (la) antigen, 10 and the focus of the current study, osteopontin (OPN)." Although the mechanisms by which these genes are regulated are unknown, it is plausible to consider that SMC diversity plays a role, since plaque SMCs show a spectrum of phenotypes ranging from well differentiated (ie, containing abundant smooth muscle contractile proteins) to relatively undifferentiated (ie, containing little contractile apparatus but increased protein synthetic machinery), with the latter being present in the greatest numbers and commonly implicated in lesion progression. 12Using a differential cloning strategy, we have identified OPN, as well as several other genes (eg, collagen 1 [o-l], elastin), that are overexpressed in the rat neointima in vivo and that distinguish rat vascular SMC phenotypes in vitro.1314 OPN is an arginine-glycineaspartate-containing acidic phosphoprotein normally restricted to bone matrix, kidney, and epithelial lining cells and has been implicated in bone morphogenesis, tumor metastasis, bacterial resistance, immune function, and renal physiology. 15 In vitro, OPN serves as an adhesive substrate for both vascular smooth muscle and endothelial...

Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients

“…In our study, OPN was observed in macrophages, aSMApositive cells, endothelial cells, lipid core and calcified nodules, as reported previously. 3 However, the distribution of trOPN was distinct. TrOPN was not observed in macrophage-rich areas in the absence of intraplaque vessels, which suggests a close relationship between trOPN and intraplaque hemorrhage and vessels.…”

“…23 In our study, heparin might have suppressed plasma OPN cleavage by thrombin, which may explain why the increase in OPN levels did not correlate with post-procedural trOPN levels. Endothelial cells also produce OPN, 3 and the stress of the catheter and contrast medium could have induced OPN secretion from endothelial cells. Other inflammatory cytokines, such as interleukin-6, matrix metalloproteinases 3 and 9, high-sensitivity CRP and tumor necrosis factor, were also measured as reported previously.…”

“…2 OPN is secreted by many cell types, such as lymphocytes, macrophages, endothelial cells and vascular smooth muscle cells, 3 and exacerbates inflammation through the recruitment of monocyte macrophages and the regulation of cytokine production in macrophages, dendritic cells and T-cells. [4][5][6] Clinically, plasma OPN levels have a positive relationship with carotid atherosclerosis in patients with essential hypertension (EHT) and an absence of cardiovascular disease.…”

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

“…However, the induction of OPN has been a well-known function of Aldo in various organs. In other words, the production of OPN was increased under various inflammatory conditions, such as that involved with calcified aortas, 17 coronary artery plaques 26 and obesity. 27 In addition, it was reported that in OPN-defective mice, fibrosis and arteriosclerotic changes were attenuated.…”

Osteopontin expression and its possible functions in the aortic disorders and coronary artery disease

“…Besides, OPN expression was directly correlated with the expression of CD44s proteins [7]. In coronary patients, the overexpressions of OPN were typically related to the presence and extent of atherosclerotic plaques and calcification lesions in the aorta [8,9]. OPN levels were significantly more increased in patients with aortic dissection, aortic aneurysm, and coronary artery disease.…”