Isamu Miyamori

Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. However, the site of their production has so far been believed to be only the adrenal cortex. Here, we show direct evidence that vascular cells per se are aldosteronogenic, possessing their own system that responds to the steroid. Using polymerase chain reaction after reverse transcription, the CYP11B2 mRNA encoding the key enzyme for the biosynthesis of aldosterone was detected in both endothelial cells and smooth muscle cells cultivated from human pulmonary artery. The aldosterone receptor (type 1 mineralocorticoid receptor) gene was also found to be expressed in smooth muscle cells and, to a lesser extent, in endothelial cells. CYP11B2 gene expression in smooth muscle cells was stimulated by angiotensin II, the effector peptide of the renin-angiotensin system. Furthermore, the angiotensin II-induced increase in [3H]leucine incorporation in smooth muscle cells was significantly enhanced by aldosterone but inhibited by ZK 91587, a type 1 mineralocorticoid receptor antagonist. This may indicate that vascular aldosterone participates in the angiotensin II-induced hypertrophy of vascular smooth muscle cells. The present study therefore provides the starting point for a novel understanding of the molecular basis of vascular remodeling and hypertension.

INTRODUCTION: Idiopathic ventricular outflow tract tachycardia or premature ventricular contractions (OT-VTs) can originate from several different sites in the outflow tract, including the left ventricular (LV) endocardium and epicardium. The aims of this study were (1) to develop an ECG algorithm to predict the origin of OT-VT and (2) to test prospectively the accuracy of the algorithm. METHODS AND RESULTS: An algorithm was developed by correlating the 12-lead ECG findings with the catheter ablation site in 80 patients with OT-VT. The ECG characteristics of the QRS complex during the arrhythmia were analyzed. The catheter sites were verified by multi-plane fluoroscopy. The outflow tract was classified into six subdivisions: right ventricular (RV) septum, RV free wall, RV near the His-bundle region, LV endocardium, left sinus of Valsalva (LSV), and LV epicardium remote from the LSV. An OT-VT originating from the LV epicardium remote from the LSV was defined as an OT-VT in which the earliest ventricular activation was recorded at the LSV and radiofrequency ablation from the LSV failed. This algorithm subsequently was tested prospectively in 88 patients. Overall sensitivity was 88% and specificity was 95%. The positive and negative predictive values were 88% and 96%, respectively. CONCLUSION: We describe a new ECG algorithm having a high sensitivity and specificity to identify the optimal ablation site for idiopathic ventricular outflow tachycardia or premature ventricular contractions.

UNLABELLED: Recent reports have indicated the value and limitations of (18)F-FDG PET and (201)Tl SPECT for determination of malignancy. We prospectively assessed and compared the usefulness of these scintigraphic examinations as well as (18)F-FDG PET delayed imaging for the evaluation of thoracic abnormalities. METHODS: Eighty patients with thoracic nodular lesions seen on chest CT images were examined using early and delayed (18)F-FDG PET and (201)Tl-SPECT imaging within 1 wk of each study. The results of (18)F-FDG PET and (201)Tl SPECT were evaluated and compared with the histopathologic diagnosis. RESULTS: Fifty of the lesions were histologically confirmed to be malignant, whereas 30 were benign. On (18)F-FDG PET, all malignant lesions showed higher standardized uptake value (SUV) levels at 3 than at 1 h, and benign lesions revealed the opposite results. Correlations were seen between (18)F-FDG PET imaging and the degree of cell differentiation in malignant tumors. No significant difference in accuracy was found between (18)F-FDG PET single-time-point imaging and (201)Tl SPECT for the differentiation of malignant and benign thoracic lesions. However, the retention index (RI) of (18)F-FDG PET (RI-SUV) significantly improved the accuracy of thoracic lesion diagnosis. Furthermore, (18)F-FDG PET delayed imaging measuring RI-SUV metastasis was useful for diagnosing nodal involvement and it improved the specificity of mediastinal staging. CONCLUSION: No significant difference was found between (18)F-FDG PET single-time-point imaging and (201)Tl SPECT for the differentiation of malignant and benign thoracic lesions. The RI calculated by (18)F-FDG PET delayed imaging provided more accurate diagnoses of lung cancer.

The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. In vitro and in vivo studies have shown that VLDL receptor binds triglyceride (TG)-rich lipoproteins but not LDL, and functions as a peripheral remnant lipoprotein receptor. VLDL receptor is expressed abundantly in fatty acid-active tissues (heart, skeletal muscle and fat), the brain and macrophages. It is likely that VLDL receptor functions in concert with lipoprotein lipase (LPL), which hydrolyses TG in VLDL and chylomicron. In contrast to the LDL receptor, VLDL receptor binds apolipoprotein (apo) E2/2 VLDL particles as well as apoE3/3 VLDL, and the expression is not down-regulated by intracellular lipoproteins. Recently, various functions of the VLDL receptor have been reported in lipoprotein metabolism, metabolic syndrome/atherosclerosis, cardiac fatty acid metabolism, neuronal migration and angiogenesis/tumor growth. Gene therapy of VLDL receptor into the liver showed a benefit effect for lipoprotein metabolism in both LDL receptor knockout and apoE mutant mice. Beyond its function as a peripheral lipoprotein receptor, possibilities of its physiological function have been extended to include signal transduction, angiogenesis and tumor growth.

Angiotensin I (Ang I), Ang II, angiotensinogen, and renin are formed locally in the vasculature. We undertook this study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an angiotensin-converting enzyme inhibitor, Ang II, or potassium on aldosterone production in vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 hours. The perfusate was collected and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system. The fraction corresponding to synthetic aldosterone was collected and analyzed by mass spectrometry. The aldosterone concentration in the perfusate from the adrenalectomized rats and rats treated with an angiotensin-converting enzyme inhibitor was measured using radioimmunoassay after HPLC separation. The mass spectra of synthetic aldosterone and aldosterone isolated from the perfusate of rat mesenteric arteries were identical. Aldosterone production in the mesenteric arteries of adrenalectomized rats was increased and of rats treated with an angiotensin-converting enzyme inhibitor was reduced compared with that of controls. Ang II (1.9 x 10(10) mol/L) and potassium (6.0 mmol/L) increased aldosterone production in mesenteric arteries. This study shows that the rat mesenteric artery produces aldosterone and that the intravascular renin-angiotensin-aldosterone system may contribute to vascular tone.