Hyaluronic acid as a potential mediator of the inflammatory responses associated with atherosclerosis

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Project objective

The processes involved in the formation of atherosclerotic lesions include: i) the proliferation of vascular smooth muscle cells (VSMC), macrophages and possibly Iymphocytes; ii) the formation by VSMC of a connective tissue matrix comprising elastic fibre proteins, collagen and proteoglycans; and iii) the accumulation of lipid and mostly free and esterified cholesterol in the surrounding matrix and the associated cells. Among several growth factors and cytokines platelet-derived growth factor (PDGF) has been shown to be essentially involved in atherosclerosis. It is generally not expressed in the normal artery, whereas it is upregulated in lesions of atherosclerosis. We have recently shown that PDGF stimulates human VSMC, in culture, to secrete a specific form of hyaluronic acid (HA), with molecular mass of 340 kDa, which has a potent antiproliferative activity on VSMC. These results suggest that VSMC in response to PDGF are capable of controlling their own growth by the synthesis of this specific 340-kDa HA molecule which may be involved in the regulation of the local inflammatory processes associated with atherosclerosis. In the present study we are going to investigate: a) The molecular mechanism by which the 340-kDa HA inhibits VSMC proliferation. b) The effect of the 340kDa HA on VSMC migration and c) The presence of this molecule in the different layers of human atheromatic arterial walls as compared with normal arteries. Such information will highlight a further fascinating facet of the complex regulatory network controlling VSMC growth and migration in vessels and will have farreaching implications for our understanding of the pathophysiological mechanisms contributing to the formation of atherosclerotic lesions.

Original text from CORDIS.

Participants

• Universität Wien · WienCoordinatorAustria
• Not availableCity levelGreece

Links

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