Objectives Chlorogenic acid (CGA) is an antioxidant dietary factor. We investigated the effects of CGA on endothelial cell dysfunction in diabetic mice and the mechanistic role of nuclear factor erythroid-related factor 2 (Nrf2) in the antioxidant effect of CGA. Methods Diabetic (db/db) mice were fed normal chow or chow containing 0.02% CGA for 12 weeks. Human umbilical vein endothelial cells (HUVECs) and mouse aortas were treated with normal or high glucose. Results CGA treatment induced upregulation of Nrf2 in HUVECs in a dose-dependent manner. CGA pretreatment prevented reactive oxygen species generation and preserved nitric oxide bioavailability in HUVECs and aortas from wild-type but not Nrf2−/− mice. CGA improved endothelium-dependent relaxation in high glucose-treated aortas from wild-type and db/db mice, but not Nrf2−/− mice. Dietary CGA improved endothelium-dependent relaxation in db/db mice. Conclusions CGA ameliorates endothelial dysfunction in diabetic mice through activation of the Nrf2 anti-oxidative pathway.
There is a lack of studies that evaluate the association between normal weight central obesity and subsequent outcomes in patients with premature acute coronary syndrome (ACS). We evaluated 338 consecutive male patients (aged ≤ 55 years) with premature ACS. The primary outcomes were all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). We compared the hazard ratios (HRs) in patients with and without normal weight central obesity using multivariable Cox proportional hazard models. All-cause mortality (16.8%) of patients with normal weight central obesity was much higher than those (7.1%) without normal weight central obesity ( P = .008). The incidence of MACCE in patients with and without normal weight central obesity were 40.7 and 23.6% ( P = .001), respectively. After multivariable adjustment, the risks of all-cause mortality and MACCE were significantly higher in patients with normal weight central obesity than those without normal weight central obesity (adjusted HR: 1.83; 95% confidence interval [CI]: 1.04-3.31; P = .004 and adjusted HR: 1.62; 95% CI: 1.18-2.27; P = .017, respectively). In conclusion, the risks of all-cause mortality and MACCE were significantly higher in male patients with premature ACS with normal weight central obesity than in those without normal weight central obesity.
Background: Antithrombotic therapy is a cornerstone of acute myocardial infarction (AMI) treatment and is thought to be associated with an increased risk of chronic subdural hematoma (CSDH). However, no wellestablished model exists to predict subsequent antithrombotic treatment outcomes after CSDH in patients with recent AMI. We aimed to identify a prognostic model to predict the 6-month outcome of treatment with antithrombotic therapy. Methods: This multicenter retrospective analysis involved 553 patients with recent AMI with antithrombotic-related CSDH. Several candidate clinical variables and biomarkers were examined in the training cohort (Chengdu training cohort; n=368). Patients with unfavorable outcomes had experienced at least 1 of the following: major adverse cardiovascular events (MACE), recurrence, or a modified Rankin scale (mRS) score of 2 to 6. To develop a 6-month outcome prediction model, three approaches were used: (I) a demographic variable model, (II) a clinical marker model and (III) a decision-driven model. A clinical outcome prediction model based on the superior predictors was assessed by logistic regression analysis. The nomogram for the final model was internally validated using a bootstrap procedure and externally validated in an independent cohort (Anhui cohort; n=185). Results: Model A produced 7 predictors of unfavorable outcomes, while models B and C yielded 2 and 1 predictors, respectively. The areas under the curve (AUC) increased from 0.743 [model A; 95% confidence interval (CI): 0.680-0.782] to 0.889 (model A + B + C; 95% CI: 0.851-0.916). The final prediction model included age, systolic blood pressure (SBP), body mass index (BMI), the Glasgow Coma Scale (GCS), the estimated glomerular filtration rate (eGFR), the early resumption of antithrombotic therapy, hematoma thickness and the presence of abdominal obesity, frailty and previous bleeding. Internal and external validation of the selected final model revealed adequate C-statistics and calibration slope values (internal validation: 0.81 and 0.78; external validation: 0.80 and 0.76, respectively).Conclusions: This model provided a risk stratification tool to predict unfavorable outcomes in patients with recent AMI with antithrombotic-related CSDH. Because the study was based on ten readily practical and available variables, it may be widely applicable to guide management and complement clinical assessment.
The Tiaopi Huxin recipe (TPHXR) is widely used in traditional Chinese medicine for the clinical treatment of coronary heart disease. However, the mechanism of TPHXR treatment of atherosclerosis (AS) has not been fully elucidated. In this study, we have aimed to explore the potential antiatherosclerotic effect of TPHXR and its underlying mechanisms. Male ApoE knockout (ApoE−/−) mice were fed a high‐fat diet for 12 weeks and were randomly divided into four groups: the control group, and the low‐dose, medium‐dose, and high‐dose TPHXR groups. The nitric oxide (NO) levels in arterial tissue and human umbilical vein endothelial cells (HUVECs) were measured by diaminofluorescein‐2 diacetate staining. Vasorelaxation of mice aorta was performed by wire myograph. Inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), hs‐CRP, IL‐6, and IL‐1β, in mice plasma were analyzed by enzyme‐linked immunosorbent assay. Western blot analysis was applied to observe protein expression. Oil Red O staining was utilized for the quantification of atherosclerotic plaques. Results showed that 4 weeks of high‐ and medium‐dose TPHXR treatment by oral gavage reduced atheromatous lesions in ApoE −/− mice. The high‐ and medium‐dose TPHXR treatment, but not the low‐dose treatment, promoted eNOS phosphorylation, increased NO levels and improved endothelium‐dependent vasorelaxation in ApoE −/− mice. High‐ and medium‐dose TPHXR, but not low‐dose TPHXR, decreased the expression of cav‐1, NF‐κB p50, NF‐κB p65, ICAM1, VCAM‐1, TNF‐α, IL‐6, and IL‐1β in the vasculature of ApoE −/− mice. Enzyme‐linked immunosorbent assay analysis indicated that high‐ and medium‐dose TPHXR decreased the levels of TNF‐α, IL‐6, hs‐CRP, and IL‐1β. In conclusion, our findings show that TPHXR improved the endothelial function and reduced atheromatous lesions in ApoE −/− mice. This result may be due to the decreased expression of caveolin‐1 and NF‐κB and, hence, the attenuated inflammatory response in AS mice vasculature. TPHXR may represent a promising intervention in patients with AS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.