Giant congenital coronary artery fistula to left brachial vein clearly detected by multidetector computed tomography.

Coronary artery fistulas (CAF) are a rare anomaly in which there is communication between a coronary artery and a cardiac chamber or another vascular structure. A giant congenital CAF to the left brachial vein was identified clearly by multidetector computed tomography (MDCT) in an 84-year-old woman who presented with orthopnea and continuous murmur. Electrocardiogram was almost normal, but chest X-ray showed marked cardiomegaly with pulmonary congestion. Transthoracic echocardiography showed that the wall motion of the left ventricle (LV) was normal, but with an abnormal cavity behind the LV. CAF was suspected and coronary angiography revealed that the CAF originated from the right coronary artery (RCA), connected to the giant vessel. However, because the drainage site was not clearly detected, MDCT was performed and it became clear that the CAF originated from the RCA. The left circumflex artery flowed into the giant vessel, and drained to the left brachial vein.

Vascular inflammation is negatively autoregulated by interaction between CCAAT/enhancer-binding protein-delta and peroxisome proliferator-activated receptor-gamma.

CCAAT/enhancer-binding proteins (C/EBPs) upregulate transcription of various inflammatory cytokines and acute phase proteins, such as interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, and cyclooxygenase-2. Recent studies have demonstrated that peroxisome proliferator-activated receptor (PPAR)-gamma is present in atherosclerotic lesions, and negatively regulates expression of these genes. Interestingly, PPAR-gamma gene promoter has tandem repeats of C/EBP-binding motif, and C/EBP-delta plays a pivotal role in transactivation of PPAR-gamma gene. It has been well known that the interaction between C/EBPs and PPAR-gamma plays a central role in maintaining adipocyte differentiation and glucometabolism; however, the relationship between PPAR-gamma and C/EBPs in the vessel wall remains unclear. In the present study, we showed that a high level of C/EBP-delta expression induced by inflammation positively regulated transcription and protein expression of PPAR-gamma in vascular smooth muscle cells (VSMCs). On the other hand, PPAR-gamma ligands troglitazone, pioglitazone, and 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited IL-1beta-induced IL-6 expression at a transcriptional revel in VSMCs. Functional promoter analysis revealed that PPAR-gamma ligands inhibited IL-1beta-induced transactivation of IL-6 gene via suppression of not only nuclear factor-kappaB but also C/EBP-DNA binding. Moreover, PPAR-gamma ligands suppressed protein expression and transcription of C/EBP-delta through dephosphorylation of signal transducer and activator of transcription 3. These findings strongly suggest that C/EBP-delta is negatively autoregulated via transactivation of PPAR-gamma. This feedback mechanism probably downregulates transcription of inflammatory cytokines and acute phase proteins, and modulates inflammatory responses in the early process of atherosclerosis.

Soluble Fas ligand and atherosclerosis in hypertensive patients.

BACKGROUND: The Fas-Fas ligand (FasL) system is involved in apoptosis in many types of cells. Recently, the expression of FasL on endothelial cells was reported. FasL is cleaved by a metalloproteinase and released in serum as soluble FasL (sFasL). Vasoactive substances, including metalloproteinase, are modulated by endothelial dysfunction. Advanced atherosclerosis and impaired endothelial function are seen in hypertensive patients. The inflammatory response has an important role in the development of atherosclerosis, whereas C-reactive protein (CRP) is associated with the presence and severity of atherosclerosis. OBJECTIVE: To measure the intima-media thickness of the common carotid artery and evaluate the relationship between atherosclerosis and serum sFasL concentrations in hypertensive patients. PATIENTS AND MAIN OUTCOME MEASURES: Forty-seven patients with hypertension participated in the study. The intima-media thickness of the common carotid artery was evaluated by ultrasound imaging. Serum concentrations of sFasL were measured by enzyme-linked immunosorbent assay. RESULTS: Intima-media thickness correlated positively with age (r = 0.362, P = 0.012) and sFasL concentrations (r =0.332, P = 0.022), and negatively with creatinine clearance (r = -0.399, P = 0.0055). A general linear model analysis with atherosclerotic risk factors and sFasL revealed that age, sFasL, high-density lipoprotein-cholesterol and systolic blood pressure were significantly associated with intima-media thickness. Furthermore, we demonstrated that serum sFasL is directly associated with CRP concentration (r = 0.316, P = 0.030). CONCLUSIONS: These results indicated that serum sFasL concentration is associated with atherosclerosis and inflammatory disease, in patients with hypertension.

A case of metastatic extra-adrenal pheochromocytoma 12 years after surgery.

At the age of 53, a 65-year-old man had been diagnosed with extra-adrenal pheochromocytoma in the retroperitoneum and underwent total tumorectomy. Afterward, he had his serum catecholamine periodically measured in an outpatient clinic. In February 1999, 12 years after surgery, he complained of lower left abdominal pain. Computed tomography and magnetic resonance imaging revealed an osteolytic lesion in thoracic vertebrae 11Th (Th 11). Although his basal serum and urine catecholamines were at normal levels, glucagon injection increased blood pressure and plasma catecholamine levels. 131I-metaiodobenzylguanidine (MIBG) scintigraphy was specifically taken up to Th 11. By bone biopsy, the osteolytic lesion in Th 11 was finally diagnosed with metastasis of pheochromocytoma. For post-operative pheochromocytoma, long-term follow-up involving biochemical tests, including serum catecholamines, and MIBG is needed.

Mechanism of oxidative stress-induced GADD153 gene expression in vascular smooth muscle cells.

Oxidative stress plays a critical role in normal functioning of cardiac and vascular cells as well as in the pathogenesis of cardiovascular disease. Growth arrest and DNA damage-inducible gene 153 (GADD153), which is upregulated by oxidative stress, regulates the cell cycle and apoptosis. Previously an AP-1 was reported to contribute significantly to GADD153 gene transcriptional activation by oxidative stress. Recently, we have reported that GADD153 gene promoter activity is negatively regulated by nuclear factor 1 (NF1), in vascular smooth muscle cells (VSMCs). The aim of this study was to elucidate the roles of AP-1 and NF1 in GADD153 gene induction by oxidative stress in VSMCs. H(2)O(2) induced GADD153 mRNA and reduced NF1 mRNA expression. In the electromobility shift assay, H(2)O(2) induced AP-1-binding activity and reduced NF1-binding activity. Overexpression of NF1 significantly suppressed the induction of the GADD153 gene after treatment with H(2)O(2). These results revealed that induction of the GADD153 gene by oxidative stress is regulated mainly by two nuclear factors, NF1 and AP-1.