Masataka Horiuchi

Vasculoprotective roles of neuronal nitric oxide synthase

Nitric oxide (NO) has multiple important actions that contribute to the maintenance of vascular homeostasis. NO is synthesized by three different isoforms of NO synthase (NOS), all of which have been reported to be expressed in human atherosclerotic vascular lesions. Although the regulatory roles of endothelial NOS (eNOS) and inducible NOS (iNOS) on the development of atherosclerosis have been described, little is known about the role of neuronal NOS (nNOS). Here, we show that nNOS also exerts important vasculoprotective effects in vivo. In a carotid artery ligation model, nNOS gene‐deficient (nNOS‐KO) mice exhibited accelerated neointimal formation and constrictive vascular remodeling caused by blood flow disruption. In a rat balloon injury model, the selective inhibition of nNOS activity potently enhanced vasoconstrictor responses to a variety of calcium‐mobilizing stimuli, suppressed tissue cGMP concentrations, a marker of vascular NO production, and exacerbated neointimal formation. In both models, nNOS was absent before injury and was up‐regulated only after the injury, and was predominantly expressed in the neointima and medial smooth muscle cells. These results provide the first direct evidence that nNOS plays important roles in suppressing arteriosclerotic vascular lesion formation in vivo.

Examination of Stent Deformation and Gap Formation after Complex Stenting of Left Main Coronary Artery Bifurcations Using Microfocus Computed Tomography

BACKGROUND Fluoroscopy and intravascular ultrasound (IVUS) lack sufficient resolution for assessing the results of complex stenting in true bifurcation lesions. OBJECTIVES After diverse bifurcation stenting at the left main coronary artery (LM) bifurcation model, the results were examined using microfocus computed tomography (MFCT). METHODS The strut distribution of three kinds of stents deployed on a straight vessel segment was investigated. Classical crush, double kissing (DK)-double crush, and culotte stenting were performed on a three-dimensional (3D) LM model. The results were assessed using cross-sectional, longitudinal, and 3D reconstruction views of MFCT. RESULTS Nonuniform strut distribution was observed in a corrugated stent design deployed on a straight vessel segment. Following classical crush stenting, a relatively large gap at the nonmyocardial site was observed in the corrugated stents. When the guidewire recrossed outside the ostium of the crushed side branch stent, kissing balloon inflation caused further crushing of the stent at the more distal segment. The dilated strut rose up from the main vessel bed after the first kissing balloon inflation in DK crush stenting; the advantage of DK would be cancelled after main vessel stenting due to recrushing the raised strut. The culotte stenting with closed-cell stents showed the restriction of the expansion at the branch ostium when it was dilated with a 3.5-mm balloon. The culotte stenting with open-cell-based stents showed a good stent apposition except for a tiny gap and small metallic carina at the distal bifurcation. CONCLUSION MFCT analysis in the 3D phantom model is useful to assess the structural deformation of the stents and gap on vessel wall coverage after complex stenting at the LM bifurcation.

Upregulation of Vascular Extracellular Superoxide Dismutase in Patients With Acute Coronary Syndromes

Objective—We examined the vascular expression levels of extracellular superoxide dismutase (EC-SOD), a major antioxidant enzyme in the cardiovascular system, in patients with acute coronary syndromes. Methods and Results—Twenty-one consecutive patients with acute myocardial infarction (AMI), 14 patients with unstable angina, 11 patients with stable angina, and 20 control subjects were studied. The levels of vascular EC-SOD expression were assessed by the difference in plasma EC-SOD concentrations before and after intravenous heparan injection. In the patients with AMI, vascular EC-SOD expression (ng/mL) was significantly higher on day 1 after the onset of AMI (148±10) as compared with the control subjects (116±6, P <0.05). The vascular EC-SOD expression returned to the normal range on day 7 (104±8), and that level persisted thereafter. The vascular EC-SOD expression was also significantly higher in the patients with unstable angina (160±13) than in those with stable angina (122±10) or in the controls (116±6) (P <0.05 each). Moreover, in the patients with AMI, higher levels of vascular EC-SOD expression on day 1 were significantly associated with smaller myocardial infarct size (P <0.05). Conclusions—This is the first clinical demonstration showing that vascular EC-SOD may be upregulated in acute coronary syndromes in humans in vivo. EC-SOD may play an important protective role against increased oxidative stress during acute ischemic coronary events.