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 vasoconstrictors, augmented the production of the precursor of tissue procollagenase / promatrixmetalloproteinase-1 (proMMP-1) and DNA synthesis in cultured human aortic smooth muscle cells (SMC) significantly compared with that in untreated SMC. Moreover, AGII and TXA(2) stimulated hydrolysis of phosphoinositides and subsequent formation of inositol triphosphate (IP3), leading to an increase in the intracellular free Ca2+ concentration. These results suggest that the production of proMMP-1 increased by AGII and TXA(2) in intimal SMC in relation to cell proliferation plays a role in arterial reconstruction in vascular diseases.