We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not met-hemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.

Aim: Platelet-derived microparticles (PDMPs) play roles in normal hemostatic responses to vascular injury because they possess prothrombinase activity. Although the most widely used method for studying PDMP is flow cytometry, we previously developed an enzyme-linked immunosorbent assay (ELISA) method as an easier and more reproducible PDMP assay. The purpose of this study was to use various clinical settings to verify whether this ELISA method can produce equivalent results to flow cytometry for PDMP. Methods: We performed a large-scale clinical study for various thrombotic and subatherothrombotic diseases using an ELISA kit. The study group included 692 patients with cerebral infarction, heart failure, acute coronary syndrome or diabetes mellitus. Results: When baseline PDMP values in the various diseases were compared with those in healthy controls, significant differences were noted in all cases. There were significantly elevated levels of PDMPs in diabetic patients with complications but no thrombosis. When baseline PDMP values in cerebral infarction were compared within the subclassifications, atheroma and other types of infarction exhibited significantly elevated PDMP levels compared with lacunar infarction. Cerebral infarction exhibited a significant change in PDMPs after therapy compared with the baseline (before therapy), but not in acute coronary syndrome and heart failure. The ELISA method exhibited results almost identical to flow cytometry for PDMP in various atherothrombotic diseases.

SUMMARYThe objective of the present study was to determine if carvedilol protects against myocardial degeneration and fibrotic change, and reduces mortality in TO2 hamsters.Carvedilol was administered intraperitoneally to 8 week-old TO2 hamsters for 21 weeks at a dose of 11 mg/kg/day. There were 15 TO2 hamsters in the carvedilol group (group C) and 10 in the untreated group (group N). The control group consisted of 11 Fb hamsters (group F). The mortality rate was determined from the number of surviving hamsters after 29 weeks. Myocardial fibrosis was evaluated by MRI and histopathological examination. EF and LVDd were determined by echocardiography at 8 and 29 weeks, while the MRI score was calculated at 29 weeks.Mortality, histopathological fibrosis, and MRI score were all lower in group C than in group N. Carvedilol had a protective effect against myocardial fibrosis and decreased the mortality rate in TO2 hamsters. ( 2-4) Following this, β-blocker therapy became used for the treatment of chronic heart failure.We previously performed MRI studies in a hamster model of cardiomyopathy (Bio 14.6 hamster) and found abnormal sites of enhancement as well as delayed enhancement. We proposed that the enhanced areas were regions of myocardial degeneration and fibrosis. 5) Carvedilol is a β-blocker that also has α-blocking and antioxidant effects, which have been shown to reduce the mortality rate of patients with moderate to severe chronic cardiac failure by 35% to 65%, in addition to also lowering the rehospitalization rate. 3,4) In the present study, we assessed the effects of carvedilol [6][7][8] in another hamster model of dilated cardiomyopathy, the BioFrom the

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These results suggest that myocardial 123I-MIBG scintigraphy is suitable for assessing cardiac sympathetic activity noninvasively in diabetic states, even in the early stages.