Etsuko Mizoguchi

Time-course of Toll-like receptor 2 expression, as a predictor of recurrence in patients with bacterial infectious diseases

The clinical course of bacterial infectious diseases is often variable, especially in elderly patients. Thus, new biological markers have been sought to predict the disease outcome. Recent studies have revealed that Toll‐like receptor (TLR) 2 and/or TLR4 on circulating monocytes are significantly up‐regulated in bacterial infections. However, the lack of reliable quantification methods hampers extensive study on the modulation of these molecules in response to the patients clinical condition. In this study, we developed a new quantitative flow cytometric analysis system for TLR2. We then carried out a longitudinal study on TLR2 expression levels on monocytes from patients suffering from bacterial infectious diseases during and after antibiotic treatment. The clinical outcome divided 37 patients into ‘cure’ (n = 24) and ‘recurrence’ (n = 13) groups. A significant difference between the two groups was recognized in the TLR2 levels just after antibiotic treatment (antibody‐binding sites/cell, 4395 ± 784 versus 5794 ± 1484, P < 0·001). The risk of recurrence was associated significantly with TLR2 (P < 0·001), but not C‐reactive protein (P = 0·351) levels assayed during the first remission. Furthermore, antibiotic effectiveness was associated inversely with TLR2 levels during antibiotic administration (P < 0·001). Taken together, TLR2 expression levels on monocytes provide critical information for planning treatment against bacterial infectious diseases.

Comparison of effect between nitrates and calcium channel antagonist on vascular function in patients with normal or mildly diseased coronary arteries

The comparative long-term antianginal efficacy of long-acting nitrates versus calcium channel antagonists remains unclear. The goal of the present study was to compare the coronary endothelial cell function and coronary artery vasoconstriction between patients with normal or mildly diseased coronary arteries treated with long-acting nitrates or calcium channel antagonists. Forty-two patients suspected to have angina pectoris and with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. All patients were suspected to have angina pectoris and were receiving either long-acting nitrates (n = 18; Nitrates group) or calcium channel antagonists (n = 24; Ca-antagonists group) for at least 1 year. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Segments that showed the greatest constrictive response to Ach were used for assessment of vasoconstriction. The percent increase in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach was significantly smaller in the Nitrates group than in the Ca-antagonists group (33% ± 74% vs 83% ± 77%, P < 0.05; −3% ± 16% vs 11% ± 12%, P < 0.01, respectively). The percent diameter reduction in the region of greatest constrictive response to Ach was significantly greater in the Nitrates group than in the Caantagonists group (44% ± 39% vs 15% ± 32%, P < 0.02). Long-term treatment with long-acting nitrates may produce less favorable effects on coronary endothelial function and the constrictive response to Ach when compared with long-acting calcium channel antagonists in patients with normal or mildly diseased coronary arteries.

Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries

BackgroundThe relationship between coronary remodeling, shear stress and endothelial function remains unclear. ObjectiveThe present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries. MethodsPatients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis ≥40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin. ResultsVessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67±70 vs. 16±75%, P<0.05) and coronary artery diameter (−7±18 vs.−32±31%, P<0.01) and also significantly smaller coronary wall shear stress (65±27 vs. 81±32 dynes/cm2, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=−0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=−0.33, P=0.19). ConclusionsEndothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.

Enjoying hobbies is related to desirable cardiovascular effects

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 ± 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% ± 77% vs 25% ± 37%, P < 0.05, 4% ± 13% vs −3% ± 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.