Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-deficient (ApoE −/− ) mice. Methods: Male ApoE −/− mice (6 weeks) were fed with a high-fat diet for 13 weeks and then randomized to the model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or the atorvastatin group (5 mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber, and foam cells to the plaque. The expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum levels of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array. Results: Tan IIA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15 ± 1.2%, HT: 12.2 ± 1.64%, MT: 13.93 ± 1.59%, MOD: 18.84 ± 1.46%, P < 0.05) or foam cells (ATO: 16.05 ± 1.26%, HT: 14.88 ± 1.79%, MT: 16.61 ± 1.47%, MOD: 22.08 ± 1.69%, P < 0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22 ± 1.91%, HT: 17.58 ± 1.33%, MT: 15.71 ± 2.26%, LT:14.92 ± 1.65%, MOD: 9.61 ± 0.7%, P < 0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88, and NF-κB p65, and serum level of MCP-1 and TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL, or TG levels between ApoE –/– mice and those treated with atorvastatin. Conclusions: These results suggest that Tan IIA could stabilize vulnerable AS plaque in ApoE −/− mice, and this anti-inflammatory and immune-regulating effect may be achieved via the TLR4/MyD88/NF-κB signaling pathway.
BackgroundPreliminary evidence based on clinical observations suggests that meditative exercise may offer potential benefits for patients with chronic heart failure (CHF). Cardiac rehabilitation (CR), as a class-IA indication in clinical practice guidelines, has been established as an effective strategy to improve quality of life and prognosis of CHF patients. Baduanjin exercise is an important component of traditional Chinese Qigong exercises. However, its benefits for CHF have not been rigorously tested. We sought to investigate whether Baduanjin, as an adjunct to standard care, improves cardiopulmonary function, exercise tolerance, and quality of life in patients with CHF caused by coronary artery disease (CAD).Methods/designIn this randomized controlled trial, 120 patients will be randomly allocated in a 1:1 ratio to Baduanjin exercise combined with conventional exercise of CR (Baduanjin exercise group) or conventional exercise of CR alone (conventional exercise group). In addition to conventional physical activity, participants in the Baduanjin exercise group will participate in a 45-min Baduanjin exercise training session twice a week, for 12 weeks. The primary outcome is walking distance in the 6-min Walk Test (6MWT), and the secondary outcomes are peak oxygen uptake (VO2 peak), ventilatory anerobic threshold (VAT), The minute ventilation to carbon dioxide production relationship (VE/VCO2 slope), left ventricular end-diastolic volume index (LVEDVi), left ventricular ejection fraction (LVEF), quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), amino-terminal pro-brain natriuretic peptide (NT-proBNP), hs-CRP, heart rate variability (HRV), New York Heart Association (NYHA) classification, and major adverse cardiovascular events.DiscussionThis is the first trial to evaluate the effects of a Baduanjin exercise-based CR program on cardiopulmonary function and exercise tolerance in ischemic CHF patients. If successful, it will prove the value of Baduanjin exercise in improving cardiopulmonary function and exercise tolerance in patients with ischemic heart failure on phase-II CR, and may further develop a Chinese Qigong exercise-based CR framework.Trial registrationClinicalTrials.gov, ID: NCT03229681. Registered retrospectively on 23 July 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2759-4) contains supplementary material, which is available to authorized users.
Background: Resistance training (RT), as part of exercise prescriptions during cardiac rehabilitation for patients with cardiovascular disease (CVD), is often used as a supplement to aerobic training (AT). The effectiveness and safety of RT has not been sufficiently confirmed for coronary heart disease (CHD).Objective: To provide updated evidence from randomized clinical trials (RCTs) on efficacy and safety of RT for the rehabilitation of CHD.Method: Three English and four Chinese electronic literature databases were searched comprehensively from establishment of each individual database to Dec, 2020. RCTs which compared RT with AT, no treatment, health education, physical therapy, conventional medical treatment (or called usually care, UC) in CHD were included. Methodological quality of RCTs extracted according to the risk of bias tool described in the Cochrane handbook. The primary outcomes were the index of cardiopulmonary exercise testing and the quality of life (QOL). The secondary outcomes included the skeletal muscle strength, aerobic capacity, left ventricular function and structure.Results: Thirty-right RCTs with a total of 2,465 participants were included in the review. The pooling results suggest the RT+AT is more effective in the cardiopulmonary exercise function (peak oxygen uptake, peak VO2) [MD, 1.36; 95% CI, 0.40–2.31, P = 0.005; I2 = 81%, P < 0.00001], the physical score of QOL [SMD, 0.71; 95% CI, 0.33–1.08, P = 0.0003; I2 = 74%, P < 0.0001] and global score of QOL [SMD, 0.78; 95% CI, 0.43–1.14, P < 0.0001; I2 = 60%, P = 0.03], also in the skeletal muscle strength, the aerobic capacity and the left ventricular ejection fraction (LVEF) than AT group. However, there is insufficient evidence confirmed that RT+AT can improve the emotional score of QOL [SMD, 0.27; 95% CI, −0.08 to 0.61, P = 0.13; I2 = 70%, P = 0.0004] and decrease left ventricular end-diastolic dimension (LVEDD). No significant difference between RT and AT on increasing peak VO2 [MD, 2.07; 95% CI, −1.96 to 6.09, P = 0.31; I2 = 97%, P < 0.00001], the physical [SMD, 0.18; 95% CI, −0.08 to 0.43, P = 0.18; I2 = 0%, P = 0.51] and emotional [SMD, 0.22; 95% CI, −0.15 to 0.59, P = 0.24; I2 = 26%, P = 0.25] score of QOL. Moreover, the pooled data of results suggest that RT is more beneficial in increasing peak VO2 [MD, 3.10; 95% CI, 2.52–3.68, P < 0.00001], physical component [SMD, 0.85; 95% CI, 0.57–1.14, P < 0.00001; I2 = 0%, P = 0.64] and the emotional conditions [SMD, 0.74; 95% CI, 0.31–1.18, P = 0.0009; I2 = 58%, P = 0.12] of QOL and LVEF, and decreasing LVEDD than UC. Low quality evidence provided that RT had effect in decreasing rehospitalization events than UC [RR, 0.33, 95% CI 0.17 to 0.62, P = 0.0006; I2 = 0%, P = 0.64]. There is no significant difference in the safety of RT compared to AT.Conclusions: RT combined with AT is more beneficial than AT alone for CHD. RT can effectively improve the capacity of exercise and the QOL compared with UC. But the difference between RT and AT is still unknown. More high-quality and large-sample studies are needed to confirm our findings.
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