These results suggest that cerivastatin can directly modulate the biology of the AAA wall and suppress MMP-9 production in the AAA wall by inhibiting the activation of neutrophils and macrophages, indicating that statin therapy could be useful for the prevention or treatment of AAA.

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Background-Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD.On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). Methods and Results-To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (nϭ10) and control aortas (nϭ12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (PϽ0.01) and AT2R expression was significantly increased (PϽ0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (PϽ0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (PϽ0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients. Conclusions-Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD. (Circulation. 2001;104[suppl I]:I-282-I-287.)

Aims HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. Methods We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group ( n = 15) or cerivastatin group ( n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. Results There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h ( P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endotheliumindependent dilatation of brachial artery was not altered. Conclusions A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.

Wave intensity (WI) is a new hemodynamic index, which is defined as (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time derivatives of blood pressure and velocity, respectively. Arterial WI in normal subjects has two positive sharp peaks. The first peak occurs during early systole when a forward-traveling compression wave is generated by the left ventricle. The magnitude of this peak increases markedly with an increase in cardiac contractility. The second peak, which occurs towards the end of systole, is caused by generation of a forward-traveling expansion wave by the ability of the left ventricle to actively stop aortic blood flow. The interval between the R wave of the ECG and the first peak of WI (R-1st peak interval) and the interval between the first and second peaks (1st-2nd interval) are approximately equal to the preejection period and left ventricular ejection time, respectively. Using a combined Doppler and echo-tracking system, we obtained carotid arterial WI noninvasively. We examined the characteristics of WI in 11 patients with mitral regurgitation (MR) before and after surgery, and 24 normal volunteers. In the MR group before surgery, the second peak was decreased and the (1st-2nd interval)/(R-R interval) ratio was reduced, compared with the normal group (140 +/- 130 vs 750 +/- 290mmHg m/s3. P < 0.0083; 20.7% +/- 3.4% vs 26.7% +/- 2.8%, P < 0.083). There were no significant differences in the first peak between the normal group and the MR group before and after surgery. The second peak in the MR group was increased significantly (P < 0.016 vs before surgery) to 1,150 +/- 830mmHg m/s3 in the early period after surgery (stage I), and to 1,090 +/- 580mmHgm/s3 in the late period after surgery (stage II). These values did not differ significantly from that of the normal group. At stage I, the (R-1st peak interval)/ (R-R interval) ratio was increased from 13.4% +/- 2.7% to 20.6% +/- 5.6% (P < 0.016 vs before surgery). At stage II, this ratio decreased to 16.2% +/- 2.8% (P < 0.016 vs stage I). but was still significantly higher than that before surgery. The (1st-2nd interval)/(R-R interval) ratio increased significantly after surgery (P < 0.016 vs before surgery) to values (27.0% +/- 4.5% at stage I and 28.9% +/- 2.6% at stage II) which did not differ significantly from that of the normal group. The recovery of the second peak after surgery suggests that the left ventricle had recovered the ability to actively stop aortic blood flow. Wave intensity is useful for analyzing changes in the working condition of the heart.