The peak levels of CD14(+)CD16(-) monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.

MDCT can identify differences in plaque morphologies between TCFA and non-TCFA. From our results, MDCT may provide for the noninvasive assessment of vulnerable plaque.

No abstract

Abstract-We investigated whether aliskiren, a direct renin inhibitor, improves NO bioavailability and protects against spontaneous atherosclerotic changes. We also examined the effects of cotreatment with aliskiren and valsartan, an angiotensin II receptor blocker, on the above-mentioned outcomes. Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), aliskiren, valsartan, or aliskiren plus valsartan for 8 weeks. Then, acetylcholine-induced NO production was measured as a surrogate index of endothelium protective function, and both superoxide and vascular peroxynitrite were measured. Tetrahydrobiopterin in aortic segments was assessed by high-performance liquid chromatography with fluorescence detection. Plaque area was quantified by histology. Increase in plasma NO concentration in response to intra-aortic acetylcholine infusion was significantly greater in all of the test groups than in controls. Aliskirenϩvalsartan cotreatment increased acetylcholine-induced NO by 6.2 nmol/L, which was significantly higher than that with either aliskiren or valsartan alone. Vascular superoxide and peroxynitrite levels were both significantly higher in controls and significantly lower in the aliskirenϩvalsartan group than in the aliskiren or valsartan group. The highest tetrahydrobiopterin levels were observed after aliskirenϩvalsartan cotreatment. Histology of the thoracic aorta revealed that the plaque area was significantly decreased with combination therapy compared with monotherapy. Treatment with a direct renin inhibitor has protective effects on endothelial function and atherosclerotic changes. Furthermore, cotreatment with a direct renin inhibitor and an angiotensin II receptor blocker has additive protective effects on both. T he renin-angiotensin system (RAS) activity may be a key factor in the pathophysiology and development of hypertension, atherosclerosis, heart failure, and renal disease in a substantial number of patients. 1,2 However, it remains unclear whether angiotensin-converting enzyme (ACE) inhibitors and angiotensin (Ang) II receptor blockers (ARBs) have fully delivered the expected reduction in cardiovascular risk. In fact, optimized RAS suppression is difficult to achieve with currently available antihypertensive agents, partly because ACE inhibitors and ARBs both activate compensatory feedback mechanisms that result in renin release and increase plasma renin activity (PRA). [3][4][5] In contrast, renin inhibitors neutralize any compensatory increase in PRA and prevent the formation of both Ang I and Ang II. 6 Aliskiren, the first in a new class of orally effective renin inhibitors for the treatment of hypertension, is a potent and specific inhibitor of human renin in vitro with an IC 50 value in the low nanomolar range. 7,8 Studies in healthy volunteers have shown that aliskiren treatment leads to dose-dependent reductions in PRA and Ang II levels. 9 Early clinical trials in hypertensive patients showed that this drug provided antihypertensive efficacy comparable to those of th...