Objective-Production of several metalloproteinases (MMPs) from smooth muscle cells (SMCs) and macrophages causes matrix destruction and atherosclerotic plaque instability. Statins, which inhibit HMG-CoA reductase and hence cholesterol and isoprenoid synthesis, stabilize plaques. We investigated whether statins inhibit MMP secretion from SMCs and macrophages. Methods and Results-We used human saphenous vein and rabbit aortic SMC and foamy macrophages from cholesterol-fed rabbits. Cerivastatin (50 nmol/L) inhibited inducible MMP-1, -3, and -9 secretion from human SMC by 52Ϯ19%, 71Ϯ18%, and 73Ϯ17%, respectively (PϽ0.01, nϭ3). Similar dose-related effects of cerivastatin (50 to 500 nmol/L), simvastatin (1 to 20 mol/L), and lovastatin (5 to 20 mol/L) were consistent with their relative potencies against HMG-CoA reductase. Statins also inhibited inducible MMP-1, -3, and -9 and constitutive MMP-2 secretion but not TIMP-1 or -2 secretion from rabbit SMC. Statins also dose-dependently inhibited MMP-1, -3, and -9 secretion from rabbit foam cells; cerivastatin (50 nmol/L) inhibited by 68Ϯ18%, 74Ϯ14%, and 74Ϯ14%, respectively (PϽ0.01, nϭ4 [3][4][5][6] Overexpression of MMPs, including MMP-1, MMP-3, and MMP-9, has been demonstrated in human and animal atherosclerotic plaques, [7][8][9][10][11][12][13][14][15][16] where it is colocalized with morphological and mechanical determinants of plaque rupture. MMPs together can catalyze the complete destruction of interstitial collagen, 17 which is the main component of fibrous caps responsible for their tensile strength. Loss of collagen leads to structural weakness and less resistance to the mechanical stresses imposed during systole. 18 This results ultimately in plaque rupture, the key event in triggering coronary thrombosis and hence acute coronary syndromes such as unstable angina and myocardial infarction. 19 Expression of MMPs-1, -3, and -9 is upregulated in cells present in atheromas, including endothelial cells, 20 VSMCs, 21-25 and macrophages. 26 -29 Inflammatory mediators, including interleukin-1 (IL-1), CD-40 ligand, and tumor necrosis factor-␣, upregulate MMP activity in vascular cells, especially in combination with platelet-derived growth factor (PDGF) or basic fibroblast growth factor. 23,25 Tissue inhibitors of metalloproteinases (TIMPs) are a family of naturally occurring specific inhibitors of MMPs whose activity in atherosclerotic plaques seems to correlate with decreased MMP activity 30,31 and hence reduced matrix remodelling.Statins are a structurally related group of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are widely used to treat hyperlipidemia. Their use is associated with significant reduction of adverse coronary events, including myocardial infarction, and a marginal regression of plaque size. 32,33 Furthermore, recent studies, both in vitro and in vivo, have suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction. [33][34][35][36] These pleiotropic effects of statins are mediate...

The aim of this study was to evaluate the usefulness of two-dimensional echocardiography in observing the left ventricular apical thin point (LVATP) and to view the change in thickness and width of the LVATP during the cardiac cycle. Transthoracic echocardiography was performed in 32 healthy adult volunteers to observe the LVATP in an apical three-chamber view. The width and thickness of the LVATP were measured at the end-diastole as well as at the end-systole. With two-dimensional echocardiography, the LVATP could be clearly shown. The width of the LVATP at the end-diastole and end-systole was 3.3 mm +/- 1.4 mm versus 0.9 mm+/-0.4 mm, P < 0.001; the thickness of the LVATP at the end-diastole and end-systole was 1.7 mm +/- 0.6 mm versus 1.8 mm +/- 0.8 mm, P > 0.05. The LVATP can be viewed with two-dimensional echocardiography; the LVATP changes significantly in width during the cardiac cycle, whereas the thickness of the LVATP changes insignificantly.