Lubiprostone as a potential therapeutic agent to improve intestinal permeability and prevent the development of atherosclerosis in apolipoprotein E-deficient mice.

The interaction between atherosclerosis and commensal microbes through leaky gut syndrome (LGS), which is characterized by impaired intestinal permeability and the introduction of undesired pathogens into the body, has not been fully elucidated. Our aim was to investigate the potential role of a ClC-2 chloride channel activator, lubiprostone, which is reported to have beneficial effects on LGS, in the development of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. After a 15-week feeding period of a Western diet (WD), ApoE-/- mice were treated with a Western-type diet (WD) alone or WD with oral supplementation of lubiprostone for 10 weeks. This feeding protocol was followed by experimental evaluation of LGS and atherosclerotic lesions in the aorta. In mice with lubiprostone, in vivo translocation of orally administered 4-kDa FITC-dextran was significantly improved, and RNA expression of the epithelial tight junction proteins, Zo-1 and occludin, was significantly up-regulated in the ileum, compared to the WD alone group, suggesting a possible reversal of WD-induced intestinal barrier dysfunction. As a result, WD-induced exacerbation of atherosclerotic lesion formation was reduced by 69% in longitudinally opened aortas and 26% in aortic root regions. In addition, there was a significant decrease in circulating immunoglobulin level, followed by an attenuation of inflammatory responses in the perivascular adipose tissue, as evidenced by reduced expression of pro-inflammatory cytokines and chemokines. Lubiprostone attenuates atherosclerosis by ameliorating LGS-induced inflammation through the restoration of the intestinal barrier. These findings raise the possibility of targeting LGS for the treatment of atherosclerosis.

Successful prediction of cardiovascular risk by new non-invasive vascular indexes using suprasystolic cuff oscillometric waveform analysis.

BACKGROUND: Recently, new non-invasive vascular indexes named arterial velocity pulse index (AVI) and arterial pressure volume index (API), which is evaluated by a multifunctional blood pressure monitoring device, were developed using cuff oscillometric technologies and suprasystolic cuff oscillometric wave measurement. However, although a few studies including a computational model have been performed, data on subjects with cardiovascular diseases in actual outpatient clinics remain scant. METHODS: We examined a total 252 consecutive outpatients and analyzed two vascular indexes with various clinical parameters to explore potential utilities of these two indexes in actual clinical settings. RESULTS: Although we found that two indexes were correlated with each other, the clinical implications of these indexes seemed to differ. Our analyses showed that AVI significantly correlated with augmentation index, but not with flow-mediated dilatation, and multivariate analyses suggested that enhanced AVI represents increased workload on the heart with elevated central blood pressure. In contrast, although the results of analyses performed to identify clinical parameters independently related to API were obscure and non-specific, after adjustment for multiple clinical variables, API was found to be significantly and independently associated with both Framingham Cardiovascular Risk Score and the Suita Score, suggesting that API is a useful predictor of future cardiovascular events. CONCLUSIONS: These two new vascular indexes might be useful in actual clinical settings to evaluate cardiovascular risks with various clinical backgrounds.