Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.

BackgroundLeft atrial appendage (LAA) dysfunction predisposes patients with atrial fibrillation (AF) to cardioembolic stroke. Two-dimensional (2D) speckle tracking was reported to be useful for evaluating left atrial (LA) regional function, as well as left ventricular function. However, it remains unclear whether 2D speckle tracking is useful for evaluating LAA dysfunction. Therefore, we investigated whether decreased LA strain may predict LAA dysfunction and thrombus formation in patients with acute ischemic stroke.MethodsWe performed transthoracic and transesophageal echocardiography in 120 patients (83 males, mean age 72 ± 11 years) within 7 days of onset of an acute ischemic stroke. Longitudinal LA strain was evaluated using 2D speckle tracking imaging at each LA segment, and peak systolic strain was calculated by averaging the results for each segment.ResultsForty-eight patients had LAA dysfunction as defined by the presence of LAA thrombus and/or severe spontaneous echo contrast. LA peak systolic strain was significantly decreased in patients with LAA dysfunction compared to those without (32.3 ± 13.7% vs. 12.1 ± 7.2%, p < 0.0001). LA peak systolic strain was significantly correlated with LAA emptying flow velocity (r = 0.693, p < 0.0001). The optimum LA peak systolic strain cut-off value for predicting LAA dysfunction was 19%. Multivariate logistic regression analysis showed that LA peak systolic strain was an independent predictor of LAA dysfunction (odds ratio 0.059, 95% confidence interval 0.018–0.146; p < 0.0001).ConclusionDecreased LA peak systolic strain was independently associated with LAA dysfunction in patients with acute ischemic stroke.

Elevated plasma BNP concentrations may be a reliable surrogate marker for the prediction of LAA dysfunction and cardiogenic stroke in patients with acute ischemic stroke.

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