The fibroproliferative response of arterial smooth muscle cells to ballooncatheter injury is associated with increased hyluronidase production and hyaluronan degradation

Hyalaronan (HA) is a glycosaminoglycan found in greatest amounts in the ext ra-cellular matrix of loose connective tissue. HA has been shown to be clos ely involved in arterial smooth muscle cell (ASMC) proliferation and migrat ion. No studies have examined the degradation of HA in the vessel wall duri ng proliferation of ASMC. The aim of our study was to determine whether HA degradation was modulated in the injured rat aorta with a catheter balloon. To evaluate HA degradation we quantified the activity of the enzyme which degrades HA (hyaluronidase) and determined HA molecular mass in the aorta. Aorta was analyzed in sham operated aorta (DO) and 14 (D14) days after inju ry. Intima-media wet weight and DNA content, a parameters reflecting ASMC r esponse to injury, were significantly increased at D14 (+ 35.5 and +40.8%). HA increased at D14 ( +87%) and was mainly expressed in the neointima. Hya luronidase activity also increased in the aorta at D14 ( +25.5%). In the no rmal aorta, HA was mainly present in a high molecular mass form (2000 kDa). Two low molecular mass HA were also detected (29 and < 20 kDa). At D14, th e form of 2000 kDa was dramatically increased in comparison to that in norm al aorta. In addition, the injured aorta contained a large number of low mo lecular mass form of HA. To know whether hyaluronidase production in the in jured aorta was associated with appearance of new isoforms, we determined t he molecular mass of this enzyme. Only one form of hyaluronidase (78 kDa) w as present in both groups (DO and D14). In conclusion, the proliferative re sponse of ASMC to injury in the rat was found to be associated with increas ed HA degradation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.