Anti-atherosclerotic effects of geraniin through the gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway in mice.

BACKGROUND: Cardiovascular disease is a leading cause of death, which signifies the urgent need for effective anti-atherosclerotic strategies. Gut microbiota-dependent trimethylamine-N-oxide (TMAO) is associated with atherosclerosis, and geraniin, a natural polyphenol with various biological activities, might play key role in this process. PURPOSE: We aimed to investigate the pharmacological activity of geraniin in atherosclerosis through remodeling the gut microbiota. METHODS: C57BL/6J ApoE-/- mice were administrated geraniin for 12 weeks. The colon contents were analyzed via 16S rRNA sequencing. Pathological staining was performed to evaluate the atherosclerotic characteristics. Cytokine assays detected the levels of plasma inflammatory cytokines. RAW264.7 cells were cultured in vitro and treated with TMAO. Tandem Mass Tag quantitative proteomics analysis and western blot were performed to investigate the effect of TMAO in macrophages. RESULTS: The plasma TMAO level in mice significantly decreased after geraniin intervention. The predominant intestinal microflora from geraniin-treated mice were Bacteroides (65.3%) and Firmicutes (30.6%). Pathological staining demonstrated that administration of geraniin attenuated atherosclerotic characteristics. After geraniin treatment, plasma levels of IL-1ß, IL-6, and TNF-α in mice were significantly reduced, and IL-10 levels were significantly increased. Proteomics analysis demonstrated the number of differentially expressed proteins after TMAO administration. In vitro study suggested that the atherogenic effect of TMAO could be attributed to changes in CD36, transmembrane protein 106a, apolipoprotein C1, macrophage scavenger receptor types I and II, and alpha-2-macroglobulin. CONCLUSION: Geraniin might be an effective prospective drug against cardiovascular diseases, and the gut microbiota is a potential target to reduce the risk of atherosclerotic disease.

Association Between Vitamin D and Hyperuricemia Among Adults in the United States.

Background: Serum uric acid can act as a risk factor for cardiovascular disease (CVD) and as antioxidant defense. Vitamin D deficiency can activate the parathyroid to induce the release of parathyroid hormone, which was thought to increase serum uric acid level, and low vitamin D status may also be associated with risk of CVD. No known studies have explored the association between serum 25(OH) D, vitamin D intake, and HU for the American population. Methods: We extracted 15,723 US adults aged 20-85 years from the National Health and Nutrition Examination Survey (NHANES) in 2007-2014. All dietary intakes were evaluated through 24-h dietary recalls. Multivariable logistic regression analysis was performed to examine the associations after adjustment for confounders. Results: Compared to the lowest quintile (Q1), for males, adjusted odds ratios (ORs) of HU in Q2 to Q4 of serum 25(OH) D levels were 0.78 (95% CI, 0.65-0.93), 0.97 (0.81-1.16), and 0.72 (0.60-0.88); ORs in Q2-Q5 of total vitamin D intake were 0.83 (0.69-0.98), 0.69 (0.58-0.83), 0.66 (0.55-0.79), and 0.59 (0.48-0.71), respectively. In females, OR was 0.80 (0.66-0.97) of serum 25(OH) D for Q3, and ORs in Q5 of total vitamin D intake were 0.80 (0.65-0.98). Conclusions: Our findings indicated that the serum 25(OH) D intakes of dietary vitamin D, supplemental vitamin D, and total vitamin D were inversely associated with HU in males. In females, a lower risk of HU with higher serum 25(OH) D, dietary vitamin D, and total vitamin D intake was found, but with no association between supplemental vitamin D intake and the risk of HU.

Effect of statin therapy on the progression of coronary atherosclerosis.

BACKGROUND: An increasing number of authors employing intravascular ultrasound (IVUS) and virtual histology (VH-IVUS) have investigated the effect of statin use on plaque volume (PV) and plaque composition. However, inconsistent results have been reported. Therefore, we conducted a meta-analysis to determine the appropriate regimen of statins to effectively stabilize vulnerable coronary plaques. METHODS: Online electronic databases were carefully searched for all relevant studies. We compared mean values of PV and plaque composition between baseline and follow-up in patients receiving statin therapy. We pooled treatment effects and calculated mean differences (MD) with the 95% confidence interval (CI) using a random-effects model. By stratified analyses, we explored the influence of clinical presentation, dose and duration of statin treatment, and low-density lipoprotein-cholesterol (LDL-C) levels on the effects of statins. RESULTS: Seventeen studies involving 2,171 patients were analyzed. Statin therapy significantly decreased PV (-5.3 mm(3); 95% CI: -3.3 mm(3) to -7.2 mm(3) P < 0.001), without heterogeneity. When considering the dose and duration of statins used, only subgroups employing a high dose and long duration demonstrated a significant reduction in PV (p < 0.001). A significant decrease in PV was noted if achieved LDL-C levels were <100 mg/dL (p < 0.001). Statin treatment could induce a twofold decrease in PV in patients with acute coronary syndrome (ACS) compared with that observed in patients with stable angina pectoris (SAP). A regressive trend was seen for necrotic core volume (MD: -2.1 mm(3); 95% CI: -4.7 mm(3) to 0.5 mm(3), P = 0.11). However, statin use did not induce a significant change for fibrotic, fibro-fatty, or dense calcium compositions. CONCLUSIONS: Our meta-analysis demonstrated that statin therapy (especially that involving a high dose and long duration and achieving <100 mg/dL LDL-C levels) can significantly decrease PV in patients with SAP or ACS. These data suggested that statins can be used to reduce the atheroma burden for secondary prevention by appropriately selecting the statin regimen. No significant change in plaque composition was seen after statin therapy.