Emodin, A Chinese Herbal Medicine, Inhibits Reoxygenation-Induced Injury in Cultured Human Aortic Endothelial Cells by Regulating the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) and Endothelial Nitric Oxide Synthase (eNOS) Signaling Pathway.

BACKGROUND Ischemia-reperfusion injury is associated with vascular dysfunction. The aim of this study was to investigate the role of emodin, a Chinese herbal medicine, in hypoxia-reoxygenation injury in cultured human aortic endothelial cells (HAECs) and its effects on the expression of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and endothelial nitric oxide synthase (eNOS) signaling pathway. MATERIAL AND METHODS An in vitro hypoxia-reoxygenation model used cultured human aortic endothelial cells (HAECs). A colorimetric method evaluated the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ). Phosphorylation of PPAR-γ and endothelial nitric oxide synthase (eNOS) were measured by Western blotting. Expression of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 were evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting. Nitric oxide (NO) production was detected by diaminofluorescein-FM diacetate (DAF-FM DA) fluorescence. Immunoprecipitation was used to evaluate the molecular coupling of heat shock protein (HSP)90 and eNOS. RESULTS Hypoxia-reoxygenation injury of HAECs reduced the activity and phosphorylation of PPAR-γ, and eNOS, NO production, and HSP90/eNOS molecular coupling in a time-dependent manner. Hypoxia-reoxygenation increased the levels of inflammatory cytokines TNF-α, IL-6, and IL-8 in a time-dependent manner. Emodin treatment recovered PPAR-γ activity and phosphorylation, eNOS phosphorylation, and HSP90/eNOS coupling in HAECS in a concentration-dependent manner, which was reversed by the PPAR-γ inhibitor GW9662, and the eNOS inhibitor, L-NAME. The recovery of HSP90/eNOS coupling by emodin was impaired by GW9662 treatment. CONCLUSIONS An in vitro hypoxia-reoxygenation (ischemia-reperfusion injury) model of induction of endothelial cell inflammatory mediators showed that emodin recovered the PPAR-γ and eNOS pathway activity.

Baicalin Suppresses Hypoxia-Reoxygenation-Induced Arterial Endothelial Cell Apoptosis via Suppressing PKCδ/p53 Signaling.

BACKGROUND This study was aimed to investigate the protective role of baicalin on vascular endothelium exposed to ischemia reperfusion injury and the involved molecular mechanisms. MATERIAL AND METHODS Cultured human arterial endothelial cells (HAECs) were exposed to hypoxia/deoxygenation (H/R). Cells were also treated with baicalin at serially diluted concentrations. Cells were also treated with PKC activator PEP005 or specific siRNA against protein kinase Cδ (PKCδ). MTT assay was used to evaluate the cell viabilities. Flow cytometry was used to detect cell apoptosis. The protein phosphorylation and expression levels were determined by Western blotting. RESULTS PKCδ-siRNA transfection increased cell viabilities and reduced cell apoptosis in HAECs exposed to H/R. Baicalin treatment preserved cell viabilities and reduced apoptosis of H/R-exposed HAECs in a concentration- dependent manner. Baicalin treatment reduced phosphorylation levels of PKCδ and p53, as well as the expression levels of active caspase3 and bax in HAECs exposed to H/R. The treatment of PKC activator PEP005 impaired the protective effects of baicalin in increasing cell viabilities and reducing apoptosis in HAECs exposed to H/R. CONCLUSIONS Baicalin exerts vascular a protective effect on HAECs exposed to H/R by reducing cell apoptosis. The PKCδ/p53 apoptotic signaling pathway was the pharmacological target of baicalin.

Effect of aerobic training on exercise capacity and quality of life in patients older than 75 years with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Limited clinical studies are available on early exercise-based cardiac rehabilitation in elderly acute coronary syndrome (ACS) patients. OBJECTIVE: To evaluate the effect of aerobic exercise on exercise capacity and quality of life (QoL) in such patients. METHODS: Seventy elderly patients with ACS undergoing percutaneous coronary intervention in Zhejiang Hospital during August 2016-June 2017 were randomly divided into the control (n = 35) or cardiac rehabilitation group (CR, n = 35). The control group was treated with standard medical treatments without exercise, whereas the CR group was treated with standard medical treatments and exercise-based cardiac rehabilitation. General information, cardiopulmonary exercise test (CPET) results, responses to QoL and mental health questionnaires, and clinical outcomes and safety were collected. RESULTS: The CR group safely finished CPET and the 12-week exercise-based cardiac rehabilitation. After the 12-week intervention, the CR group showed significant differences in maximal oxygen uptake (VO2max) and greater improvements in VO2max, compared with the control group. The CR group showed statistically significant differences in QoL and mental health compared with the control group. CONCLUSION: CPET-based exercise in cardiac rehabilitation can safely increase exercise capacity and QoL in such patients.

Effect of high-intensity interval training on cardiac structure and function in rats with acute myocardial infarct.

BACKGROUND: Exercise training is beneficial for cardiac rehabilitation. Nevertheless, few study focused on the role of high-intensity interval training (HIIT) in cardiac repair. The current study aimed to elucidate the effect of HIIT on cardiac rehabilitation and the involved mechanisms after acute myocardial infarction (MI). METHODS: A total of 65 male rats underwent coronary ligation or sham operation and were randomly assigned to 4 groups: sham (n = 10), sedentary (MI-Sed, n = 12), moderate-intensity continuous training (MI-MCT, n = 12) and HIIT (MI-HIIT, n = 12). One week after MI induction, adaptive training starts follow by formal training. After the experiment, cardiac functions were determined by echocardiography and hemodynamic measurements. Changes in infarct size, collagen accumulation, myofibroblasts, angiogenesis, inflammation level, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system (RAAS) activities were measured. Data were analyzed by one-way ANOVA. RESULTS: After MI, cardiac structure and function were significantly deteriorated. However, post-MI HIIT for 8 weeks had significantly ameliorated left ventricular end-diastolic pressure (LVEDP), LV systolic pressure (LVSP), and maximum peak velocities of relaxation (-dP/dtmax). Moreover, it preserved cardiac functions, reduced infarct size, protected the myocardium structure, increased angiogenesis and decreased the myofibroblasts and collagen accumulation. HIIT for 4 weeks had no effect on LVEDP, -dP/dtmax, infarct size and angiogenesis. Additionally, it induced inflammation response and repressed ET-1 and RAAS activities were found in myocardium and peripheral circulation after HIIT. CONCLUSION: Our results suggested that post-MI HIIT had a positive role in cardiac repair, which might be linked with the induction of inflammation and inhibition of ET-1 and RAAS activities.

Bone mineral density in older patients with chronic heart failure is related to NYHA classification: a retrospective study.

PURPOSE: Discrepant results on relationship between chronic heart failure (CHF) and bone mineral density (BMD) have been reported and little has investigated the association between bone mass loss and New York Heart Association (NYHA) classification in CHF patients. This study aimed to assess whether BMD was associated with NYHA classification in older CHF patients. METHODS: It was a retrospective study and included 1049 stable CHF patients aged over 60 years in Zhejiang Hospital. BMD and T-score at femoral neck (FN) and lumbar spines over L2-L4 regions were measured using Dual-Energy X-ray Absorptiometry. One-way ANOVA was used to compare continuous data of different NYHA functional class. Categorical variables were compared by Chi-square analysis. Pearson or Spearman correlation test was used to analyze the association between BMD and NYHA class, clinical parameters, lab data, etc. Significant variables in the correlation test (P < 0.05) were then tested by a multivariate linear regression test with stepwise subset selection to identify independent factors predicting BMD. RESULTS: There were significant differences in FN BMD and T score across NYHA class I-IV, and that L2-L4 BMD and T score in patients in NYHA class IV were significantly lower when compared with CHF participants in NYHA classes I, II, and III. Moreover, Pearson correlation test and multivariate linear regression test demonstrated that there were statistically significant correlations between bone densitometric parameters and NYHA class. CONCLUSIONS: There was a significant correlation between BMD and T-score at lumbar spines over L2-L4 and FN and NYHA class, implying that early screening and comprehensive intervention for osteoporosis (OP) might be helpful for patients with CHF.

Sleep onset latency is related with reduced bone mineral density in elderly people with insomnia: a retrospective study.

PURPOSE: Inconsistent outcome about association between insufficient sleep and bone mineral density (BMD) has been reported. The present study aimed to determine whether BMD was associated with score of Pittsburgh Sleep Quality Index (PSQI). METHODS: A total of 410 patients (mean age 81.6±5.9 years) attending our hospital for evaluation of sleep were retrospectively studied. Dual-Energy X-ray Absorptiometry was used to measure BMD and T-score at femoral neck and lumbar spines over L2-L4 regions. Subjective sleep status was evaluated by the PSQI questionnaires. The Mann-Whitney U test and chi-square analysis were used to compare continuous variables and categorical variables, respectively. Spearman correlation test was conducted to find the relationship between BMD and other clinical factors. Multinomial logistic regressions analysis was performed to analyze independent factors predicting BMD. RESULTS: Majority of the participants with osteoporosis (OP) were female and had lower body mass index (BMI) and higher sleep onset latency score. Spearman correlation test showed that gender, BMI, score of total PSQI, and sleep onset latency were significantly related to BMD and T-score in femoral neck and lumbar region L2-L4. Finally, multinomial logistic regression analysis demonstrated that gender and age were independent factors for OP and osteopenia and that after adjustment for gender, age, and BMI, sleep onset latency of <15 minutes (OR: 0.38; 95% CI: 0.15-0.96; P=0.04) and 16-30 minutes (OR: 0.37; 95% CI: 0.17-0.79; P=0.01) were less likely to have reduced BMD. CONCLUSION: There was a significant association between BMD and sleep onset latency, suggesting that, in elderly patients with sleep problem, BMD measurement and intervention for OP might be valuable.

The Salutary Influence of Forest Bathing on Elderly Patients with Chronic Heart Failure.

The aim of the current study was to test the hypothesis that forest bathing would be beneficial for elderly patients with chronic heart failure (CHF) as an adjunctive therapy. Two groups of participants with CHF were simultaneously sent to the forest or an urban control area for a four-day trip, respectively. Subjects exposed to the forest site showed a significant reduction of brain natriuretic peptide (BNP) in comparison to that of the city group and their own baseline levels. The values for the cardiovascular disease related pathological factors, including endothelin-1 (ET-1), and constituents of the renin-angiotensin system (RAS), including renin, angiotensinogen (AGT), angiotensin II (ANGII), and ANGII receptor type 1 or 2 (AT1 or AT2) in subjects exposed to the forest environment were lower than those in the urban control group. Obviously, a decreased level of inflammatory cytokines and improved antioxidant function was observed in the forest group rather than in the city group. The assessment of the profile of mood states (POMS) indicated that the negative emotional mood state was alleviated after forest bathing. As anticipated, a better air quality in the forest site was observed according to the detection of PM2.5 (particulate matter <2.5 µm) and negative ions. These results provided direct evidence that forest bathing has a beneficial effect on CHF patients, and thus may pave the way for potential development of forest bathing as an effective adjunctive therapy on cardiovascular disorders.

Validation of Veterans Specific Activity Questionnaire to assess exercise tolerance of Chinese elderly with coronary heart disease.

OBJECTIVE: The Veterans Specific Activity Questionnaire (VSAQ) has been used to assess exercise tolerance. Nevertheless, there is no validated Chinese version. The aim of this study is to determine whether a questionnaire-based method using the Chinese version of VSAQ (the modified VSAQ) is a practical tool to assess exercise tolerance of Chinese elderly with coronary heart disease. METHODS: One hundred thirty consecutive elderly patients who were diagnosed with coronary heart disease (CHD) (mean age 68.9 ± 6.0 years) referred for treadmill exercise testing (TET) for clinical reasons were included in the study. They were asked to complete a questionnaire for clinical characteristics information on age, sex, history, exercise habits, medications, the original VSAQ and the modified VSAQ. We investigated the relationship between exercise tolerance in metabolic equivalents (METs) estimated by VSAQ and that obtained by TET. RESULTS: The METs by the original VSAQ and the modified VSAQ did not difference significantly (P = 0.528). The modified VSAQ scores were significantly correlated with the METs obtained by TET (r = 0.819, 95% CI: 0.753-0.873, P < 0.01), and the scores of original VSAQ also correlated with the METs by TET (r = 0.804, 95% CI: 0.745-0.854, P < 0.01). The Bland-Altman graph analysis showed few values outside the limits of agreement, suggesting good precision between the METs estimated by questionnaire and the METs obtained by TET. CONCLUSIONS: The Chinese version of the VSAQ confirmed its validity and equivalence to the original version, especially when evaluating individuals with coronary heart disease and older adults. The results showed that the VSAQ is a valuable tool to assess the exercise tolerance.