Macrophages exposed to hypoxia secrete proteoglycans for which LDL has higher affinity

Asplund, Annika; Fridén, Vincent; Stillemark-Billton, Pia; Camejo, Germán; Bondjers, Göran

doi:10.1016/j.atherosclerosis.2010.12.017

Cited by 31 publications

(28 citation statements)

References 38 publications

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“…They promote the idea that lipid droplet formation contributes to the pro-atherogenic effects of FFA on LDL [66]. Most of the lipids found in atherosclerotic plaques are present in lipid droplets and LDL derived small lipid droplets are prominent in atherosclerotic lesions [67]. Modifications such as oxidation, lipolysis and proteolysis are prerequisites for droplet fusion.…”

Section: Atherosclerosis Formationmentioning

confidence: 99%

LDL as a Cause of Atherosclerosis

Tomkin

Owens²

2012

TOATHERTJ

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The low density lipoprotein particle is the major transporter of cholesterol around the body and has been shown to be a strong independent risk factor for atherosclerotic events. This review discusses the normal and abnormal metabolism of low density lipoprotein (LDL). Mechanisms by which LDL causes atherosclerosis are discussed with particular reference to the importance of alteration in LDL composition including attachment of other proteins to the circulating LDL particle.

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Section: Atherosclerosis Formationmentioning

confidence: 99%

LDL as a Cause of Atherosclerosis

Tomkin

Owens²

2012

TOATHERTJ

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“…While accumulation of versican during the inflammatory response can originate in the stromal connective tissue, a number of past as well as more recent studies have identified versican as a gene which is upregulated in monocytes in a number of pro-inflammatory states, such as myocardial infarction (Toeda et al, 2005), coronary stenosis (Wingrove et al, 2008), autoimmunity (Masuda et al, 2013; Olsen et al, 2004; Shou et al, 2006), and in response to pro-inflammatory stimulants such as lipopolysaccharide (LPS) (Lang et al, 2002) and hypoxia (Asplund et al, 2011; Asplund et al, 2009). In addition, the versican gene is differentially expressed in M1 macrophages, as opposed to M2 macrophages, as they differentiate from monocytes (Asplund et al, 2011; Martinez et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the versican gene is differentially expressed in M1 macrophages, as opposed to M2 macrophages, as they differentiate from monocytes (Asplund et al, 2011; Martinez et al, 2006). Recent studies by our group have shown that versican mRNA, along with mRNA from other HA binding proteins such as TSG-6 and IαI, is upregulated as monocytes differentiate into macrophages (Chang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Versican and the control of inflammation

2014

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Versican is an extracellular matrix (ECM) proteoglycan that interacts with cells by binding to non-integrin and integrin receptors and to other ECM components that associate with the cell surface. Recent studies have shown also that versican interacts with myeloid and lymphoid cells promoting their adhesion and production of inflammatory cytokines. Versican is produced by stromal cells, as well as leukocytes, and is markedly increased in inflammation. Inflammatory agonists, such as double-stranded RNA mimetics (e.g., poly I:C), stimulate stromal cells, such as smooth muscle cells and fibroblasts, to produce fibrillar ECMs enriched in versican and hyaluronan (HA) that interact with leukocytes promoting their adhesion. Interference with the incorporation of versican into this ECM blocks monocyte adhesion and dampens the inflammatory response. Tumor cells also express elevated levels of versican which interact with myeloid cells to promote an inflammatory response, through stimulating cytokine release, and metastasis. In addition, myeloid cells, such as macrophages in tumors, synthesize versican which affects tumor cell phenotypes, inflammation, and subsequent metastasis. Versican, by binding to hyaluronan, influences T lymphocyte phenotypes and in part controls the ability of these cells to synthesize and secrete cytokines that influence the immune response. Collectively, these studies indicate that versican as an ECM molecule plays a central role in inflammation and as a result it is emerging as a potential target promising wide therapeutic benefits.

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“…119 It is present in the intima and adventitia of most arteries and veins, and it is synthesized by vascular smooth muscle cells as well as endothelial cells, myofibroblasts, and macrophages. 120 Versican interacts with hyaluronan and link protein to form high molecular weight stable aggregates. These complexes create a reversibly compressive compartment and provide a swelling pressure within the ECM that is compensated by collagen and elastic fibers.…”

Section: 73-118mentioning

confidence: 99%