EFFECT OF ANGIOTENSIN-II AND THROMBOXANE A2 ON THE PRODUCTION OF MATRIX METALLOPROTEINASE BY HUMAN AORTIC SMOOTH-MUSCLE CELLS

Angiotensin II (AGII) and thromboxane A(2) (TXA(2)), potent vasoconstr ictors, augmented the production of the precursor of tissue procollage nase / promatrixmetalloproteinase-1 (proMMP-1) and DNA synthesis in cu ltured human aortic smooth muscle cells (SMC) significantly compared w ith that in untreated SMC. Moreover, AGII and TXA(2) stimulated hydrol ysis of phosphoinositides and subsequent formation of inositol triphos phate (IP3), leading to an increase in the intracellular free Ca2+ con centration. These results suggest that the production of proMMP-1 incr eased by AGII and TXA(2) in intimal SMC in relation to cell proliferat ion plays a role in arterial reconstruction in vascular diseases.