Michihiko Inoue

Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial interaction

Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily, which is expressed in vascular endothelial cells. Previous studies have demonstrated that ESAM regulates angiogenesis, endothelial permeability, and leukocyte transmigration. However, little is known concerning the role of ESAM in atherosclerosis. In this study, we assessed the effects of ESAM inactivation on atherosclerosis in mice. ESAM-/- mice were bred with apoE-/- mice to generate double knockout mice, and the aortic lesion size of apoE-/- and ESAM-/-apoE-/- mice was compared histologically. Although plasma cholesterol levels were higher in ESAM-/-apoE-/- mice, the lesion size was markedly smaller than in apoE-/- mice. ESAM-/-apoE-/- mice exhibited a decrease in the number of vasa vasorum and macrophages in the vessel wall. In vitro adhesion assays showed that THP-1 cells, which did not express ESAM, bound to the ESAM-coated culture plates, suggesting that ESAM may interact with heterophilic ligand(s) on monocytes. Moreover, downregulation of ESAM by siRNA in the endothelial monolayer diminished transendothelial migration of THP-1 cells. In conclusion, ESAM inactivation can reduce susceptibility to atherosclerosis by inhibiting plaque neovascularization and macrophage infiltration into the atheroma.

The effect of poloxamer 407 on the functional properties of HDL in mice

Objectives  There is an inverse relationship between high‐density lipoprotein (HDL) and heart disease. HDL possesses not only both antioxidant and anti‐inflammatory properties, but also anti‐thrombotic and endothelial function‐promoting qualities. However, it is not only the serum concentration of HDL that is important, but also the ‘functional’ quality of the HDL. The objective was to determine the functional status of HDL in a well‐established mouse model of dyslipidaemia and atherosclerosis induced by the administration of a block copolymer (poloxamer 407; P‐407).

Ventricular tachycardia in patients with idiopathic dilated cardiomyopathy is associated with delayed enhancement MRI

of PSVT in the Korean population is limited. In this study, we sought to investigate the differing mechanisms of PSVT according to age and gender in Korean patients. Methods: Database of 3176 patients diagnosed with PSVT excluded atrial flutter or atrial fibrillation and referred for electrophysiologic study from 1986 to 2004 was retrospectively analyzed. The mechanisms of PSVT were classified as: WPW syndrome(WPW), AVRT due to concealed bypass tract(CBT), atrioventricular nodal reentrant tachycardia(AVNRT), atrial tachycardia(AT). Results: The mean age was 40.7 16.0(1-90) and 53.3% of the patients were males. The mean age of females was significantly higher than males.(43.0 16.1 vs 38.6 15.6, p 0.001) Overall, the dominant mechanism of tachycardia was AVRT at 62.6%(WPW: 31.1%, CBT: 31.5%) compared to AVNRT at 34.1% and AT at 3.1%. This was mainly due to the predominance of AVRT(74.2%) in males. The mechanisms of PSVT differed according to gender with 63.2%(1257/1988) of AVRT patients being males where as 64.6%(700/1084) of the AVNRT patients were females. The distribution of PSVT mechanisms differed according to gender. In males, the proportion of AVNRT:CBT:WPW was 22.7%:36.1%:38.1%, whereas in females the proportion was 47.2%:26.3%: 23.0%. Age had a significant influence upon the mechanism of PSVT in both genders with an increasing proportion of AVNRT and a decreasing proportion of AVRT in older age groups. AVRT was the dominant mechanism of PSVT in all age groups for males, where as AVNRT was the dominant mechanism of PSVT for females over 50 years of age. Conclusions: The mechanism of PSVT differs significantly according to age and gender. This may be due to increased degeneration of accessory pathway with age and difference in the conduction properties of the accessory pathway according to gender. In Koreans, the overall dominant mechanism of PSVT was AVRT mainly due to it a greater male population.