A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration |
| |
Authors: | Papakonstantinou E; Karakiulakis G; Eickelberg O; Perruchoud AP; Block LH; Roth M |
| |
Institution: | Department of Pharmacology, School of Medicine, Aristotle University, 54006 Thessaloniki, Greece, Department of Research, University Hospital of Basel, 4031 Basel, Switzerland and Department of Internal Medicine IV, University Hospital Vienna, Austria. |
| |
Abstract: | The formation of atherosclerotic lesions is characterized by invasion of
vascular smooth muscle cells (VSMC) into the tunica intima of the arterial
wall and subsequently by increased proliferation of VSMC, a process
apparently restricted to the intimal layer of blood vessels. Both events
are preceded by the pathological overexpression of several growth factors,
such as platelet-derived growth factor (PDGF) which is a potent mitogen for
VSMC and can induce their chemotaxis. PDGF is generally not expressed in
the normal artery but it is upregulated in atherosclerotic lesions. We have
previously shown that PDGF-BB specifically stimulates proliferating VSMC to
secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence
regarding the biological functions of this glycan. We observed that HA-340
inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent
manner and enhanced the PDGF-dependent invasion of VSMC through a basement
membrane barrier. These effects were abolished following treatment of
HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent
invasion of VSMC coincided with increased secretion of the 72-kDa type IV
collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid
inhibitor of matrix metalloproteinases. HA-340 did not exert any
chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF
gradient. In human atheromatic aortas, we found that HA- 340 is expressed
with a negative concentration gradient from the tunica media to the tunica
intima and the atheromatic plaque. Our findings suggest that HA-340 may be
linked to the pathogenesis of atherosclerosis, by modulating VSMC
proliferation and invasion.
|
| |
Keywords: | |
本文献已被 Oxford 等数据库收录! |
|