Cell surface heparan sulfate proteoglycans and lipoprotein metabolism

Kolset, S O; Salmivirta, Markku

doi:10.1007/s000180050031

Cited by 67 publications

(54 citation statements)

References 97 publications

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“…In another model, HSPGs retain BMP antagonists such as noggin and establish inverse gradients of BMP activity (20). HSPGs have a relatively rapid turnover rate (23) and mediate internalization of a diverse array of extracellular ligands including FGF2 (24), Chordin (a BMP antagonist) (25), lipoproteins (26), and viral particles (27). Here we demonstrate that HSPGs can mediate the sequestration and internalization of BMP2, thus offering an additional mechanism by which HSPGs could regulate BMP morphogenetic gradients.…”

Section: Discussionmentioning

confidence: 64%

Heparan Sulfate Proteoglycans (HSPGs) Modulate BMP2 Osteogenic Bioactivity in C2C12 Cells

Jiao

Billings

O’Connell

et al. 2007

Journal of Biological Chemistry

145

131

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Cell surface heparan sulfate proteoglycans (HSPGs) have been implicated in bone morphogenetic protein (BMP)-mediated morphogenesis by regulating BMP activity and gradient formation. However, the direct role of HSPGs in BMP signaling is poorly understood. Here we show that HSPGs directly regulate BMP2-mediated transdifferentiation of C2C12 myoblasts into osteoblasts. HSPGs sequester BMP2 at the cell surface and mediate BMP2 internalization. Depletion of cell surface HSPGs by heparinase III treatment or decreased glycosaminoglycan chain sulfation with sodium chlorate enhances BMP2 morphogenetic bioactivity. The addition of exogenous heparin, a widely used anticoagulant, reduced BMP2 signaling. Our results suggest that cell surface HSPGs mediate BMP2 internalization and modulate BMP2 osteogenic activity.

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Section: Discussionmentioning

confidence: 64%

Heparan Sulfate Proteoglycans (HSPGs) Modulate BMP2 Osteogenic Bioactivity in C2C12 Cells

Jiao

Billings

O’Connell

et al. 2007

Journal of Biological Chemistry

145

131

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“…Some findings suggest that heparin interacts directly with the TG lipases and/or competes for binding sites on cell-surface HSPG. 28 Findings from other studies indicate that heparin can act through protein kinase and calcium signaling pathways to stimulate HL release. 29 HDL-dependent HL displacement is regulated by interactions between HL and HDL and is affected by both the lipid and the apolipoprotein composition of HDL.…”

Section: Displacement Of Hspg-bound Hlmentioning

confidence: 98%

Hepatic Lipase, High Density Lipoproteins, and Hypertriglyceridemia

Chatterjee

Sparks

2011

The American Journal of Pathology

107

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Hepatic lipase (HL) is a lipolytic enzyme that contributes to the regulation of plasma triglyceride (TG) levels. Elevated TG levels may increase the risk of developing coronary heart disease, and studies suggest that mutations in the HL gene may be associated with elevated TG levels and increased risk of coronary heart disease. Hepatic lipase facilitates the clearance of TG from the very low density lipoprotein (VLDL) pool, and this function is governed by the composition and quality of high density lipoprotein (HDL) particles. In humans, HL is a liver resident enzyme regulated by factors that release it from the liver and activate it in the bloodstream. HDL regulates the release of HL from the liver and HDL structure controls HL transport and activation in the circulation. Alterations in HDL-apolipoprotein composition can perturb HL function by inhibiting the release and activation of the enzyme. HDL structure may therefore affect plasma TG levels and coronary heart disease risk. Triglycerides and Heart DiseaseElevated plasma triglyceride (TG) levels have been viewed as a risk factor for coronary heart disease (CHD) for more than a decade.1,2 Plasma TG levels are regulated by both synthesis and degradation of both very low density lipoprotein (VLDL) and chylomicron particles. The clearance of TG-rich lipoproteins from the circulation is controlled by the actions of lipoprotein lipase (LPL) and hepatic lipase (HL) and by the interlipoprotein exchange of TG by cholesteryl ester transfer protein. Lipoprotein lipase is the predominant TG lipase and is responsible for hydrolyzing TG in chylomicrons and VLDL, whereas HL is both a phospholipase and a TG lipase and plays an important role in HDL metabolism and in the conversion of VLDL to LDL.3 Single nucleotide polymorphisms (SNPs) in the HL gene (LIPC) have been shown to associate with plasma lipid concentrations and increased CHD risk. 4,5 Hepatic lipase deficiency is a result of relatively rare LIPC mutations that give rise to a loss in circulating HL activity (due to impaired secretion or inactive enzyme) and cause an increase in TG-rich HDL and VLDL remnants and increased CHD risk.

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“…123 Furthermore, shed HS has the ability to activate a variety of antigen-presenting cells (APCs) and may also promote the development of the T-helper (Th) 1 type response seen in allograft rejection. 124 Altogether, the evidences support the hypothesis that HSs has an important and extensive role in homeostasis and inflammation.…”

Section: Role Of Ecm In Cav and Atherosclerosismentioning

confidence: 99%

Allograft Vasculopathy Versus Atherosclerosis

Rahmani¹,

Cruz²,

Granville³

et al. 2006

Circulation Research

295

215

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Abstract-Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure.Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular type of coronary atherosclerosis, referred to as cardiac allograft vasculopathy (CAV). Although the exact pathogenesis of CAV remains to be established, there is strong evidence that CAV involves immunologic mechanisms operating in a milieu of nonimmunologic risk factors. The immunologic events constitute the principal initiating stimuli, resulting in endothelial injury and dysfunction, altered endothelial permeability, with consequent myointimal hyperplasia and extracellular matrix synthesis. Lipid accumulation in allograft arteries is prominent, with lipoprotein entrapment in the subendothelial tissue, through interactions with proteoglycans. The apparent endothelial "intactness" in human coronary arteries of the transplanted heart suggest that permeability and function of the endothelial barrier altered. Various insults to the vascular bed result in vascular smooth muscle cell (SMC) activation. Activated SMCs migrate from the media into the intima, proliferate, and elaborate cytokines and extracellular matrix proteins, resulting in luminal narrowing and impaired vascular function. Arteriosclerosis is a broad term that is used to encompass all diseases that lead to arterial hardening, including native atherosclerosis, postangioplasty restenosis, vein bypass graft occlusion, and CAV. These diseases exhibit many similarities; however, they are distinct from one another in numerous ways as well. The present review summarizes the current understanding of the risk factors and the pathophysiological similarities and differences between CAV and atherosclerosis. (Circ Res. 2006;99:801-815.)

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Cell surface heparan sulfate proteoglycans and lipoprotein metabolism

Cited by 67 publications

References 97 publications

Heparan Sulfate Proteoglycans (HSPGs) Modulate BMP2 Osteogenic Bioactivity in C2C12 Cells

Heparan Sulfate Proteoglycans (HSPGs) Modulate BMP2 Osteogenic Bioactivity in C2C12 Cells

Hepatic Lipase, High Density Lipoproteins, and Hypertriglyceridemia

Allograft Vasculopathy Versus Atherosclerosis

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