ABSTRACT
Anomalous origin of the left coronary artery from the right sinus of Valsalva is a rare anomaly known to cause sudden death in young competitive athletes. We report a case of 58-year-old male who was admitted to our hospital because of acute coronary syndrome. Emergency coronary angiography documented a critical stenosis in the right coronary artery. A cardiologist implanted a stent with good angiographic result. It was not possible to place a catheter in left coronary artery ostium at normal position. The patient was diagnosed to have an anomalous origin of the left coronary artery arising from the right sinus of Valsalva, passing between the aorta and the main pulmonary artery by coronary 3 dimensional computed tomography angiography (3D-CTA). After a stent insertion, he still had angina. Further examination of the left coronary artery including intravascular ultrasound revealed a hard plaque in the left main trunk as the culprit lesion. Because previous percutaneous coronary intervention was ineffective, off-pump coronary artery bypass grafting was performed using bilateral internal thoracic arterial grafts to the left anterior descending artery and the obtuse marginal branch. Postoperative 3D-CTA demonstrated patent grafts. Two years after the operation, he is free from chest discomfort.
ABSTRACT
The receptor for advanced glycation end-products (RAGE)-mediated cellular activation through the mitogen-activated protein kinase (MAPK) cascade, activation of NF-kappaB and Rho family small G-proteins, cdc42/Rac, is implicated in the pathogenesis of inflammatory disorders and tumor growth/metastasis. However, the precise molecular mechanisms for the initiation of cell signaling by RAGE remain to be elucidated. In this study, proteins which directly bind to the cytoplasmic C-terminus of RAGE were purified from rat lung extracts using an affinity chromatography technique and identified to be extracellular signal-regulated protein kinase-1 and -2 (ERK-1/2). Their interactions were confirmed by immunoprecipitation of ERK-1/2 from RAGE-expressing HT1080 cell extracts with anti-RAGE antibody. Furthermore, the augmentation of kinase activity of RAGE-bound ERK upon the stimulation of cells with amphoterin was demonstrated by determining the phosphorylation level of myelin basic protein, an ERK substrate. In vitro binding studies using a series of C-terminal deletion mutants of human RAGE revealed the importance of the membrane-proximal cytoplasmic region of RAGE for the direct ERK-RAGE interaction. This region contained a sequence similar to the D-domain, a ERK docking site which is conserved in some ERK substrates including MAPK-interacting kinase-1/2, mitogen- and stress-activated protein kinase-1, and ribosomal S6 kinase. These data suggest that ERK may play a role in RAGE signaling through direct interaction with RAGE.