Hiroshi Takaishi

High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells

In diabetes mellitus (DM), hyperglycemia causes cardiovascular lesions through endothelial dysfunction. Monocyte chemoattractant protein-1 (MCP-1) is implicated in the pathogenesis of cardiovascular lesions. By using human umbilical vein endothelial cells, we investigated the effect of hyperglycemia on MCP-1 production and its signaling pathways. Chronic incubation with high glucose increased mRNA expression and production rate of MCP-1 in a time (1-7 days)- and concentration (10-35 mM)-dependent manner. Chronic exposure to high glucose resulted in enhancement of generation of reactive oxygen species (ROS), as determined by increasing level of 2,7-dichlorofluorescein (DCF), and subsequent activation of p38 mitogen-activated protein kinase (MAPK). Neither c-Jun NH(2)-terminal kinase nor extracellular signal-regulated kinase1/2 was affected. SB203580 or FR167653, p38 MAPK specific inhibitors, completely suppressed MCP-1 expression. Catalase suppressed p38 MAPK phosphorylation and MCP-1 expression. These results indicate that hyperglycemia can accelerate MCP-1 production through the mechanism involving p38 MAPK, ROS-sensitive signaling pathway, in vascular endothelial cells.

Excessively Enlarged Right Coronary Artery Aneurysm With Intramural Thrombus Causing Recurrent Acute Coronary Syndrome

A 45-year-old man was admitted to our hospital with exertional chest pain. He had been diagnosed with membranoproliferative glomerulonephritis at the age of 20 and had undergone kidney transplantation at the age of 33. After that, he had taken some immunosuppressant drugs and steroids. Two years previously, he had presented with acute chest pain. On that occasion, cardiac enzymes were not elevated, but ECG showed the inversion of the T waves in II, III, aVF, V5, and V6 leads. We diagnosed angina pectoris and performed cardiac catheterization. Cardiac catheterization revealed a 75%-stenosed left anterior descending coronary artery (LAD) and a giant right coronary artery (RCA) aneurysm (50 mm) with intramural thrombus. Because the intravascular lumen of the RCA had been …