Background: The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2‐[1’H‐indole‐3’‐carbonyl]‐thiazole‐4‐carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T‐cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results: Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE‐treated mice exhibited significantly improved systolic function ( P <0.001) and reduced infarct size compared with control mice ( P <0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3 ⁺ (forkhead box protein P3‐positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions: Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post‐MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.

It has been long debated whether menopause itself is a risk factor for hypertension in peri-menopausal women. We aimed to assess the association between menopause and hypertension, and whether metabolic syndrome (MetS) has an influence on its effect. Data for 1502 women aged 42 to 53 from the Korean Genome and Epidemiology Study (KoGES) database were retrospectively analyzed. The KoGES database consists of 10,038 participants, of which 52.6% (5275) were female. Subjects were followed up for 4 years, and compared according to menopausal status. Additionally, 1216 non-hypertensive subjects were separately analyzed to assess whether a change in menopausal status was associated with development of hypertension. The prevalence of hypertension, diabetes, and MetS for menopausal and non-menopausal subjects at baseline was 24.4% vs. 16.7%, 5.8% vs. 2.9%, and 25.4% vs. 16.6%, respectively (p < 0.01 for all comparisons). Among non-hypertensive subjects at baseline, prevalence of hypertension at 4-year follow-up was 9.4%, 19.7%, and 13.1% for non-menopausal, those who became menopause during follow-up, and those who were menopause at baseline, respectively. Development of hypertension was positively correlated with MetS (HR 3.90, 95% CI 2.51–6.07) and increased BMI (HR 1.09, 95% CI 1.03–1.16), while association with menopause was not significant. Menopause is closely associated with increased incidence of hypertension, but the increase may not be attributable to menopause itself but to increased prevalence of MetS.

Cutaneous wound healing is delayed in patients with diabetes. Caffeic acid phenethyl ester (CAPE) has been identified as an effective constituent of propolis with improved wound healing abilities via an oxidative stress decrease. However, its impact on wound healing in diabetic models and its underlying mechanisms remain unclear. Determining the vascular endothelial growth factor (VEGF) contents in a human vascular smooth muscle cell (VSMC)-conditioned medium was assessed using human VEGF immunoassay and vascular reactivity using porcine coronary artery rings. Later, C57BL/6 or db/db mice were anesthetized, after which a 6-mm biopsy punch was manipulated for perforation via the back skin. Subsequently, CAPE was applied to the wound and changed daily. Furthermore, the injury in each mouse was digitally photographed, and the wound area was quantified. We observed that CAPE increased VEGF levels in human VSMC-conditioned medium, improved endothelium-dependent nitric oxide (NO)-mediated vasorelaxation, inhibited U46619-induced vasoconstriction porcine coronary artery, and enhanced cutaneous wound healing in the diabetic mouse model. Hence, we propose that CAPE improves wound healing in diabetic mice, which is aided by increased VEGF and NO expression.

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR’s diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.

Limited data exist on the temporal trend of major bleeding and its prediction by the Academic Research Consortium-High Bleeding Risk (ARC-HBR) criteria in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). We investigated 10-year trends of major bleeding and predictive ability of the ARC-HBR criteria in AMI patients. In a multicenter registry of 10,291 AMI patients undergoing PCI between 2004 and 2014 the incidence of Bleeding Academic Research Consortium (BARC) 3 and 5 bleeding was assessed, and, outcomes in ARC-defined HBR patients with AMI were compared with those in non-HBR. The primary outcome was BARC 3 and 5 bleeding at 1 year. Secondary outcomes included all-cause mortality and composite of cardiovascular death, myocardial infarction, or ischemic stroke. The annual incidence of BARC 3 and 5 bleeding in the AMI population has increased over the years (1.8% to 5.8%; p < 0.001). At 1 year, ARC-defined HBR (n = 3371, 32.8%) had significantly higher incidence of BARC 3 and 5 bleeding (9.8% vs. 2.9%; p < 0.001), all-cause mortality (22.8% vs. 4.3%; p < 0.001) and composite of ischemic events (22.6% vs. 5.8%; p < 0.001) compared to non-HBR. During the past decade, the incidence of major bleeding in the AMI population has increased. The ARC-HBR criteria provided reliable predictions for major bleeding, mortality, and ischemic events in AMI patients.

The current study aimed to investigate the association between serum UA levels and the mortality rate of AMI patients. We analyzed 5888 patients with successfully revascularized AMI (mean age: 64.0 ± 12.7 years). The subjects were divided into the high UA group (uric acid >6.5 mg/dL for males, >5.8 mg/dL for females) or the normal UA group based on initial serum UA level measured at admission. The primary outcome was all-cause mortality. A total of 4141 (70.3%) and 1747 (29.7%) patients were classified into the normal UA group and high UA groups, respectively. Over a median follow-up of 5.02 (3.07, 7.55) years, 929 (21.5%) and 532 (34.1%) patients died in each group. Cox regression analysis identified high UA levels as an independent predictor of all-cause mortality (unadjusted hazard ratio (HR) 1.69 [95% CI 1.52–1.88]; p < 0.001, adjusted HR 1.18 [95% CI: 1.05–1.32]; p = 0.005). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. The predictive accuracies of conventional clinical factor discrimination and reclassification were significantly improved upon the addition of hyperuricemia (C-index 0.788 [95% CI 0.775–0.801]; p = 0.005, IDI 0.004 [95% CI 0.002–0.006]; p < 0.001, NRI 0.263 [95% CI 0.208–0.318]; p < 0.001).