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.

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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...

Background-Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). One pathological study suggested that the morphologies of plaque rupture differed between rest-onset and exertion-triggered rupture in men who experienced sudden death. The aim of the present study was to use optical coherence tomography to investigate the relationship in patients with ACS between the morphology of a ruptured plaque and the patient's activity at the onset of ACS. Methods and Results-The study population was drawn from 43 consecutive ACS patients (with or without ST-segment elevation) who underwent optical coherence tomography and presented with a ruptured plaque at the culprit site. Patients were divided into a rest group and an exertion group on the basis of their activities at the onset of ACS. The thickness of the broken fibrous cap correlated positively with activity at the onset of ACS. The culprit plaque ruptured at the shoulder more frequently in the exertion group than in the rest group (rest 57% versus exertion 93%, Pϭ0.014). The thickness of the broken fibrous cap in the exertion group was significantly higher than in the rest-onset group (rest onset: 50 m [interquartile median 15 m]; exertion: 90 m [interquartile median 65 m], PϽ0.01). Conclusions-The morphologies of exertion-triggered and rest-onset ruptured plaques differ in ACS patients. Our data suggest that a thin-cap fibroatheroma is a lesion predisposed to rupture both at rest and during the patient's day-to day activity, and some plaque rupture may occur in thick fibrous caps depending on exertion levels. (Circulation. 2008;118: 2368-2373.)