Effect of DLT-SML on Chronic Stable Angina Through Ameliorating Inflammation, Correcting Dyslipidemia, and Regulating Gut Microbiota.

ABSTRACT: Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1ß, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.

The role of polysaccharide peptide of Ganoderma lucidum as a potent antioxidant against atherosclerosis in high risk and stable angina patients.

OBJECTIVES: Antioxidants can reduce oxidative radicals that affect the early phase of atherogenesis, that is endothelial dysfunction. Polysaccharide Peptide (PsP) derived from Ganoderma lucidum has an active substance in the form of ß-glucan. Previous studies have proven the PsP of Ganoderma lucidum as an effective antioxidant in atherosclerotic rats and shows no toxicity in animal model. This study aims to prove the effect of PsP as potent antioxidant in high risk and stable angina patients. METHOD: This is a clinical trial conducted to 37 high risk and 34 stable angina patients, which were determined based on ESC Stable CAD Guidelines and Framingham risk score, with pre and post test design without control group. The parameters are superoxide dimustase (SOD) and malondialdehyde (MDA) concentration, circulating endothelial cell (CEC) and endothelial progenitor cell (EPC) counts. The patients were given PsP 750mg/day in 3 divided dose for 90days. Paired t-test was performed for normally distributed data, and Wilcoxon test for not normally distributed data, and significant level of p≤0,05. RESULTS: SOD level in high risk patients slightly increased but not statistically significant with p=0,22. Level of SOD in stable angina group significantly increased with p=0,001. MDA concentration significantly reduced in high risk and stable angina patients with p=0.000. CEC significantly reduced both in high risk and stable angina patients, with p=0.000 in both groups. EPC count significantly reduced in high risk and stable angina with p=0.000. CONCLUSION: PsP of Ganoderma lucidum is a potent antioxidant against pathogenesis of atherosclerosis in stable angina and high risk patients.

Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.

BACKGROUND: Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was comparing the effect of Cratagol herbal tablet, aerobic exercise and their combination on the serum levels of Intercellular adhesion molecule (ICAM)-1 and E-Selectin in patients with stable angina pectoris. METHODS: Eighty stable angina pectoris patients aged between 45 and 65 years, were randomly divided into four groups including three experimental groups and one control group: aerobic exercise (E), Crataegus oxyacantha extract (S), aerobic exercise and Crataegus oxyacantha extract (S+E), and control (C). Blood sampling was taken 24 h before and after 12 weeks of aerobic exercise and Crataegus oxyacantha extract consumption. The results of serum levels of ICAM-1 and E-selectin were compared. RESULTS: Intergroup comparison of the data revealed a significant reduction (P <0.01) in serum levels of ICAM-1 and E-selectin in experimental groups. Analysis of data showed that the serum levels of ICAM-1 had significant difference when group S+E was compared with groups S and C, but not group E (P = 0.021, P = 0.000 and P = 0.068, respectively). Also the difference between the levels of E-selectin was significant comparing S+E and S but not E with group C (P = 0.021, P = 0.000 and P = 0.052, respectively). CONCLUSIONS: Twelve weeks effects of aerobic exercise and Crataegus oxyacantha extract consuming is an effective complementary strategy to significantly lower the risk of atherosclerosis and heart problems.

Polyunsaturated omega-3 fatty acids reduce lipoprotein-associated phospholipase A(2) in patients with stable angina.

BACKGROUND AND AIMS: Increased consumption of omega-3 polyunsaturated fatty acids (PUFA) together with lifestyle measures and medications is recommended for the prevention of cardiovascular diseases. However, the exact mechanisms underlying observed benefits are not well defined. To this aim, we evaluated the effects of omega-3 PUFA in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) on lipoprotein associated phospholipase A2 (Lp-PLA2) mass and activity and their relation to oxidized low-density lipoproteins (oxy-LDL). METHODS AND RESULTS: In a prospective, double-blind, placebo-controlled, randomized study Lp-PLA2, oxy-LDL, myeloperoxidase and interleukin-6 were determined at baseline, 3-5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 30) or placebo (n = 24). Treatment with omega-3 PUFA resulted in reduction of Lp-PLA2 mass by 10.7%, activity by 9.3 (p = 0.026 for both) and oxy-LDL by 10.9% (p = 0.014) at 30 days, with no change in myeloperoxidase and interleukin-6. Compared with placebo, patients receiving omega-3 PUFA had lower Lp-PLA2 mass by 9.42%, activity by 9.2 (p = 0.041 for both) and oxy-LDL by 12.3% (p = 0.10) after one month, but not at 3-5 days. There were no correlations between Lp-PLA2 and both myeloperoxidase and oxy-LDL throughout the study. The multivariate model showed that only treatment with omega-3 PUFA and baseline myeloperoxidase levels were independent predictors of Lp-PLA2 mass changes at one month (R(2) = 0.37, P = 0.005). CONCLUSIONS: Administration of omega-3 PUFA can decrease Lp-PLA2 in patients with stable angina undergoing PCI. This novel effect may contribute to the benefits derived from omega-3 PUF.

[A study of relationship between dialectical classification according to traditional Chinese medicine of acute coronary syndrome with serum osteoprotegerin and its ligand].

OBJECTIVE: To investigate the relationship between osteoprotegerin (OPG) system and acute coronary syndrome (ACS) and its classification according to traditional Chinese medicine (TCM). METHODS: A prospective study was conducted. The patients with ACS (n=210) and the patients with stable angina pectoris (SAP, n=200) were enrolled. The serum OPG and its ligand (sRANKL) were determined by enzyme-linked immunosorbent assay (ELISA), the OPG/sRANKL ratio was calculated, and the number of coronary vessels was involved, finally their relationship with the typing according to TCM was evaluated. One hundred and fifty non-coronary heart disease patients were enrolled as control. RESULTS: The serum OPG, OPG/sRANKL in ACS and SAP groups were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). The OPG, OPG/sRANKL in ACS groups were significantly higher than those in SAP group (both P<0.01). Serum OPG, OPG/sRANKL in ACS patients with different number of coronary vessel disease were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). OPG and OPG/sRANKL were gradually increased with increase in number of diseased coronary vessels, but the sRANKL descended (P<0.05 or P<0.01). Serum OPG and OPG/sRANKL were descended according to dialectical classification of TCM: Yang Qi weakening syndrome>Qi and blood stagnation syndrome>Qi deficiency with blood stasis syndrome>stagnation of phlegm blocks the heart-vessels syndrome>Yin deficiencies of the heart and the kidney syndrome>deficiency of both Qi and Yin syndrome, among them they were significantly higher in Yang Qi failure syndrome and Qi and blood stagnation syndromes than those of both Qi and Yin syndrome [OPG(ng/L): 621.38±32.86, 617.63±39.60 vs. 593.86±36.19, OPG/sRANKL(g/mol): 1 018.98±106.03, 1 011.27±121.61 vs. 942.16±115.82, P<0.05 or P<0.01]. Among different types of TCM in ACS group the serum sRANKL was significantly lower than that in control group (all P<0.01), but the difference among different types was not significant. CONCLUSIONS: Serum OPG, sRANKL, OPG/sRANK levels were related with incidence and severity of coronary lesions in ACS patients. Serum OPG and OPG/sRANKL ratio may have correlation with Yang Qi weakening syndrome and Qi deficiency with blood stasis syndrome.

Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: pleiotropic evidence from plasma mRNA analyses.

OBJECTIVE: Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasma mRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C). DESIGN AND METHODS: Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) mRNA levels and their protein concentrations (MCP-1, sICAM-1) were analysed before and after the treatment. Plasma vascular adhesion molecule-1 (sVCAM-1) concentrations were also analysed. RESULTS: Atorvastatin lowered plasma mRNA levels (CCL2: -31.76%, p=0.037; ICAM1: -34.09%, p<0.001) and MCP-1 protein concentration (-18.88%, p=0.008) but did not lower sICAM-1 and sVCAM-1 protein concentrations, and the decreases appeared to be independent from the lowering of LDL-C. The plasma mRNA levels correlated with their protein concentrations following statin treatment only. CONCLUSION: Our results significantly strengthen the clinical evidence in support of statin pleiotropy. Furthermore, this unique simultaneous measurement of plasma mRNAs and their protein concentrations offers an advanced non-invasive in vivo assessment of the circulation pathology.

Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life.

OBJECTIVE: This study aimed to evaluate the effects of short-term (60-d) oral supplementation with calcium fructoborate, resveratrol, and their combination on the clinical and biological statuses of subjects with stable angina pectoris. METHODS: A randomized, double-blinded, active-controlled, parallel clinical trial was conducted in three groups of subjects. Of the total number of subjects included in study (n = 166), 87 completed the 60-d test treatment study period and 29 followed in parallel their usual medical care and treatment. The primary outcomes were inflammation biomarkers (high-sensitivity C-reactive protein), left ventricular function markers (N-terminal prohormone of brain natriuretic peptide), and lipid markers (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triacylglycerols). Quality of life was assessed by the Canadian Cardiovascular Society angina class and the number of angina attacks per week. RESULTS: There was a significant decrease of high-sensitivity C-reactive protein in all groups at the 30-d and 60-d visits. This decrease was greater (39.7% at 60 d) for group 3 (calcium fructoborate), followed by group 2 (resveratrol plus calcium fructoborate, 30.3% at 60 d). The N-terminal prohormone of brain natriuretic peptide was significantly lowered by resveratrol (group 1, 59.7% at 60 d) and by calcium fructoborate (group 3, 52.6% at 60 d). However, their combination (group 2) was the most effective and induced a decrease of 65.5%. Lipid markers showed slight changes from baseline in all groups. The improvement in the quality of life was best observed for subjects who received the resveratrol and calcium fructoborate mixture (group 2). CONCLUSION: The results indicate that the combination of resveratrol and calcium fructoborate has beneficial effects in patients with angina