Endothelial cell functions are modulated by extracellular matrix which is in intimate contact with vessel wall endothelial cells (EC). In diseases such as atherosclerosis, ECM component concentrations in vessel wall intima change and that affects EC morphology and functions. For example, the concentration of hyaluronic acid (HA), a glycosaminoglycan, decreases during progression and later increases during regression of atherosclerotic plaques. In this study we examined HA-EC interactions in primary cultures of Human microvessel EC (HMVEC), Human aortic EC (HPAEC) and human umbilical vein-derived EC (HUVEC). Both HMVEC-L and HPAEC bound HA with high affinity (Kd 2 nM and 0.8 nM respectively) with 18,000 and 55,000 sites per cell, respectively. HUVEC did not bind HA. Both HMVEC-L and HPAEC displayed strong HA-mediated cell adhesion. All three EC express CD44s , a well characterized HA receptor. HA and a 10-15 disaccharide unit fragment of HA (F1), induced 1.5 and 2.3 fold increases in mitogenic response, respectively, in HMVEC-1 cells. HA and F1 induced only a marginal mitogenic response ( 1.2 fold) in HPAEC. Interestingly, both HA and F1 induced tyrosine phosphorylation of several cellular proteins in HMVEC-L in a dose and time dependent manner. These results suggest that differential responses of various ECs to HA might be important in normal vascular remodelling and vascular pathophysiology.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology