Overexpression of Hyaluronan in the Tunica Media Promotes the Development of Atherosclerosis
- 18 March 2005
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 96 (5), 583-591
- https://doi.org/10.1161/01.res.0000158963.37132.8b
Abstract
The arterial content of hyaluronan (HA) undergoes diffuse changes as part of the diabetic macroangiopathy. Because HA influences the phenotype of vascular cells in vitro such as proliferation, migration, and secretion, it is tempting to speculate that diabetes-induced hastened cardiovascular disease may be linked to the increased amount of HA. To explore the pathophysiological role of altered HA content in the arterial wall in vivo, we created transgenic (Tg) mice with HA overexpression in smooth muscle cells (SMCs) in large and small vessels, targeted by the α smooth-muscle-cell-actin (αSMA) promoter fused to the human hyaluronan synthase 2 (hHAS2) cDNA. RT-PCR demonstrated hHAS2 mRNA expression in the tunica media of large and small vessels. In situ hybridization confirmed that hHAS2 mRNA was targeted to the SMCs. The aortic HA content was elevated in the Tg mice, and by immunohistochemistry, it was seen that HA accumulated in the tunica media. The secretory profile of high- and low-molecular HA was similar in wild-type and Tg animals. Overproduction of HA in the aorta resulted in thinning of the elastic lamellae in Tg mice. Our data suggest that this may lead to increased mechanical stiffness and strength, as determined by controlled stretching until failure. Finally, overproduction of HA on the genetic background of the ApoE-deficient mouse strain promoted atherosclerosis development in the aorta. These results indicate that a single component of the diabetic macroangiopathy, diffuse accumulation of HA, accelerates the progression of atherosclerosis.Keywords
This publication has 29 references indexed in Scilit:
- Postmenopausal Hormone Therapy Is Associated With Atherosclerosis Progression in Women With Abnormal Glucose ToleranceCirculation, 2004
- Induction of Hyaluronic Acid Synthase 2 (HAS2) in Human Vascular Smooth Muscle Cells by Vasodilatory ProstaglandinsCirculation Research, 2004
- A Blocking Antibody to the Hyaluronan Receptor for Endocytosis (HARE) Inhibits Hyaluronan Clearance by Perfused LiverPublished by Elsevier BV ,2003
- Purification and molecular identification of the human hyaluronan receptor for endocytosisGlycobiology, 2002
- The involvement of the intracellular superoxide production system in hepatic ischemia-reperfusion injury: In vivo and in vitro experiments using transgenic mice manifesting excessive CuZn-SOD activityFree Radical Biology & Medicine, 2000
- Differences in Hyaluronic Acid-mediated Functions and Signaling in Arterial, Microvessel, and Vein-derived Human Endothelial CellsPublished by Elsevier BV ,2000
- THE HYALURONIC ACID RECEPTORS INDUCED BY STRETCH INJURY OF RAT BLADDER IN VIVO AND INFLUENCES SMOOTH MUSCLE CELL CONTRACTION IN VITROJournal of Urology, 1999
- Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44.JCI Insight, 1996
- Localization and solubilization of hyaluronan and of the hyaluronan-binding protein hyaluronectin in human normal and arteriosclerotic arterial wallsAtherosclerosis, 1994
- Lipoprotein-hyaluronate associations in human aorta fibrous plaque lesionsAtherosclerosis, 1980