Eiichi Okamoto

HERP1 Inhibits Myocardin-Induced Vascular Smooth Muscle Cell Differentiation by Interfering With SRF Binding to CArG Box

Objective—Myocardin is a coactivator of serum response factor (SRF) required for vascular smooth muscle cell (VSMC) differentiation. HERP1 is a transcriptional repressor, which is abundantly expressed in vascular system and is known to function as a target gene of Notch. However, the role of HERP1 in the pathogenesis of vascular lesions remains unknown. The present study characterizes the expression of HERP1 in normal and diseased vessels, and tests the hypothesis that HERP1 inhibits SRF/myocardin-dependent SMC gene expression. Methods and Results—Immunohistochemistry revealed that HERP1 and myocardin expression was localized to SMC in the neointima of balloon-injured rat aorta and in human coronary atherosclerotic lesions. Expression of both HERP1 and myocardin was elevated in cultured VSMCs compared with medial SMC. Overexpressed HERP1 inhibited the myocardin-induced SMC marker gene expression in 10T1/2 cells. HERP1 protein interfered with the SRF/CArG–box interaction in vivo and in vitro. Immunoprecipitation assays showed that HERP1 physically interacts with SRF. Conclusions—HERP1 expression was associated with the SMC proliferation and dedifferentiation in vitro and in vivo. HERP1 may play a role in promoting the phenotypic modulation of VSMCs during vascular injury and atherosclerotic process by interfering with SRF binding to CArG-box through physical association between HERP1 and SRF.

Regulated expression of the BTEB2 transcription factor in vascular smooth muscle cells: analysis of developmental and pathological expression profiles shows implications as a predictive factor for restenosis.

BackgroundWe have previously shown BTEB2, a Krüppel-like zinc finger transcription factor, to regulate expression of the SMemb/NMHC-B gene, which has been implicated in phenotypic modulation of smooth muscle cells (SMCs). The present study was done to assess the developmental and pathological expression profiles of BTEB2 and to further evaluate the clinical relevance of BTEB2 expression in human coronary artery disease. Methods and ResultsImmunohistochemistry showed developmentally regulated expression of BTEB2 with abundant expression in fetal but not in adult aortic SMCs of humans and rabbits. In balloon-injured aortas, predominant expression of BTEB2 was seen in neointimal SMCs. Atherectomy specimens obtained from primary and restenotic lesions showed predominant expression of BTEB2 to stellate SMCs. The incidence of restenosis in primary lesions was significantly higher in lesions containing BTEB2-positive cells than in lesions without (55.6% versus 25.0%, P =0.01). ConclusionsThe present study shows that BTEB2 expression is developmentally and pathologically regulated. BTEB2 is preferentially expressed in dedifferentiated or activated SMCs. Examination of human coronary artery specimens suggests that primary lesions containing BTEB2-positive cells are associated with higher risk of restenosis than BTEB2-negative lesions. These results suggest that BTEB2 can serve as a molecular marker for phenotypic modulation of vascular SMCs.

Hemoperitoneum due to a ruptured gastroepiploic artery aneurysm in systemic lupus erythematosus. A case report and literature review.

A 52-year-old woman with systemic lupus erythematosus (SLE) had a hemoperitoneum following a ruptured dissecting aneurysm of the right gastroepiploic artery. We believe this event has been reported only eight times before, but this is the first time it has been associated with SLE.

Production of radioactive endovascular stents by implantation of 133Xe ions

A coronary stent was made radioactive by implantation of 133Xe ions for the purpose of suppressing the renarrowing of the part of blood vessel in which the stent is implanted. Electrons of relatively low energies emitted in the decay of 133Xe may give an antiproliferative effect of ionizing radiation to the intimal cells within a limited range of 1 mm. A 133Xe+ beam accelerated at 40 or 60 keV was directed to several stainless steel stents mounted on a target-holder table that could revolve and move up and down to distribute the 133Xe+ ions within a stent as well as among the stents. The radioactive stents produced contained up to 100 kBq of 133Xe and were implanted into the abdominal aortas of rabbits. Neointimal thickening was analyzed by histomorphometry for samples taken 4 weeks after stent implantation. The results indicate that the radioactive stents have a potential to suppress neointimal hyperplasia in rabbits.

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p<0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p<0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r=0.80, p<0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclists heart.

Effects of enalapril on cardiac function, exercise capacity, and biochemical factors in patients with chronic heart failure

Abstract The angiotensin-converting enzyme (ACE) inhibitor enalapril was administered to 13 patients with chronic heart failure (New York Heart Association class II or III) for 12 weeks, and its effects on resting cardiac function (shown by echocardiogram), exercise capacity, and biochemical factors were investigated. Left ventricular end-diastolic and end-systolic diameters improved significantly from 60.3 ± 5.4 mm at baseline to 57.2 ± 5.7 mm after 12 weeks of treatment and from 50.2 ± 5.9 mm to 46.8 ± 5.6 mm, respectively; however left atrial dimension did not change significantly after treatment. Peak oxygen uptake also improved significantly after enalapril treatment (20.0 ± 6.9 mL/kg/min at baseline to 22.4 ± 7.6 mL/kg/min after treatment), as did anaerobic threshold by gas exchange (17.1 ± 6.4 mL/kg/min vs 18.4 ± 5.8 mL/kg/min). The serum levels of atrial natriuretic peptide and beta-endorphin decreased significantly after treatment (47.6 ± 42.1 pg/mL before vs 31.6 ± 29.2 pg/mL after treatment and 11.6 ± 3.6 pg/mL vs 5.9 ± 2.8 pg/mL, respectively). These results indicated that enalapril is useful for improving resting cardiac function, exercise capacity, and biochemical factors in patients with chronic heart failure.

Dissecting Aneurysm during Pregnancy and the Puerperium

According to Schnitker, Mandel, Hirst and their associates, approximately half of the dissecting aneurysms in women under 40 years of age are associated with pregnancy. This significant relationship between dissecting aneurysm and pregnancy has been discussed by considering hemodynamic stress and also the hormonal changes of pregnancy. In this report, we describe five patients with dissecting aneurysm during pregnancy or the puerperium, review the literature and discuss the influence of pregnancy on the pathogenesis of this disease.