Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia

Apart from ACE, various angiotensin II (Ang II)-forming serine proteinases leg, chymase, kallikrein, and cathepsin G) are known to exist in human tiss ues, but their clinical significance or the regulatory mechanisms that cont rol their activities are not well established. A recent clinical study has shown that chymase activity was significantly increased in human atheroscle rotic or aneurysmal aorta. The association between vascular Ang II-forming activities (AIIFAs) in the human internal thoracic artery (ITA) and various clinical parameters was studied with the use of ITAs obtained from 32 pati ents who underwent coronary artery bypass graft surgery, Total and ACE- and chymase-dependent AIIFAs in homogenates of ITAs were determined. Total AII FA was 8.67+/-0.86 (nmol Ang II formed . min(-1) . mg protein(-1) [U]), and approximate to 95% of the activities were due to chymase. Serum total chol esterol level, but no other risk factors, significantly correlated with chy mase- (r=0.60, P<0.001) and ACE- (r=0.35, P<0.05) dependent AIIFAs, respect ively, LDL cholesterol level was also correlated with chymase-dependent AII FAs (r=0.47, P<0.05). Mast cells identified through the use of toluidine bl ue or immunohistochemical staining appeared in the adventitia but not in th e intima or media of ITAs, Our results suggest that an increased plasma LDL cholesterol level may induce increased arterial chymase and ACE activity.