This study examined whether IGF-binding protein 5 (IGFBP5) is involved in the high glucoseinduced deteriorating effects in cardiac cells. Cardiac fibroblasts and cardiomyocytes were isolated from the hearts of 1-to 3-day-old Sprague Dawley rats. Treatment of fibroblasts with 25 mM glucose increased the number of cells and the mRNA levels of collagen III, matrix metalloproteinase 2 (MMP2), and MMP9. High glucose increased ERK1/2 activity, and the ERK1/2 inhibitor PD98059 suppressed high glucose-mediated fibroblast proliferation and increased collagen III mRNA levels. Whereas high glucose increased both mRNA and protein levels of IGFBP5 in fibroblasts, high glucose did not affect IGFBP5 protein levels in cardiomyocytes. The high glucose-induced increase in IGFBP5 protein levels was inhibited by PD98059 in fibroblasts. While recombinant IGFBP5 increased ERK phosphorylation, cell proliferation, and the mRNA levels of collagen III, MMP2, and MMP9 in fibroblasts, IGFBP5 increased c-Jun N-terminal kinase phosphorylation and induced apoptosis in cardiomyocytes. The knockdown of IGFBP5 inhibited high glucose-induced cell proliferation and collagen III mRNA levels in fibroblasts. Although high glucose increased IGF1 levels, IGF1 did not increase IGFBP5 levels in fibroblasts. The hearts of Otsuka Long-Evans Tokushima Fatty rats and the cardiac fibroblasts of streptozotocin-induced diabetic rats showed increased IGFBP5 expression. These results suggest that IGFBP5 mediates high glucose-induced profibrotic effects in cardiac fibroblasts.

Native coronary artery spasm after coronary artery bypass grafting (CABG) is scarce. It frequently causes disastrous circulatory collapse. We report a 72-yr-old male, who experienced native coronary artery spasm and grafted artery spasm following CABG, which was successfully treated with coronary angiography and intracoronary injection of nitroglycerine.

BackgroundQuadricuspid aortic valve (QAV) is a rare congenital anomaly. We investigate the mid-term results of aortic valve reconstruction by tricuspidization in patients with QAV.MethodsWe analyzed the outcome of eight consecutive patients who underwent aortic valve reconstruction surgery (AVRS) with pericardial leaflets with symptomatic quadricuspid aortic valve (QAV) disease between December 2007 and May 2012. AVRS consists of leaflet reconstruction and fixation of the sino-tubular junction in order to maintain coaptation of the new valve.ResultsSix males and two females were included; ages ranged from 19 to 63 years (mean age, 51 years). According to Hurwitz and Roberts’s classification, three patients had type A, three patients had type B, one patient had type C, and one patient had type E. All patients had significant aortic regurgitation (AR): moderate in three patients, moderate to severe in one patient, and severe in four patients. Concomitant ascending aorta wrapping with an artificial vascular graft was performed in one case. There was no occurrence of mortality during the follow-up period (42.4 ± 18.0 months). No redo-operation was required. The NYHA functional class showed improvement from 2.1 ± 0.2 to 1.1 ± 0.2 (p = 0.008). The latest echocardiograms showed AR absent or trivial in seven patients, and mild in one patient. The aortic valve orifice area index (AVAI) was 1.03 ± 0.49 cm2/m2. Compared with preoperative echocardiograms, the left ventricular (LV) ejection fraction showed improvement from 57.6 ± 17.0 to 63.7 ± 13.2% (p = 0.036); the end-diastolic and end-systolic LV dimensions showed a significant decrease, from 63.5 ± 9.6 to 49.5 ± 3.1 mm (p = 0.012) and 43.6 ± 11.8 to 32.1 ± 5.4 mm (p = 0.012), respectively.ConclusionIn patients with QAV, AVRS with tricuspidization showed satisfactory early and mid-term results. Long-term follow-up will be necessary in order to study the durability of AVRS; however, it can be considered as a potential standard procedure.

Rupture of the left ventricle after mitral valve replacement, although infrequent, may be a highly lethal complication. This report describes the early diagnosis and successful repair of rupture of atrioventricular groove in an elderly patient who underwent mitral valve replacement.

Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.