The Critical Effect of Bile Acids in Atherosclerosis.

ABSTRACT: Atherosclerosis (AS) is one of the most common cardiovascular diseases and is the leading cause of arteriosclerotic cardiovascular disease. Bile acids are not only the products of cholesterol metabolism, but also an important class of signaling molecules. Bile acids exert their biological effects through the bile acid receptor signaling pathways. Bile acid receptors are widely distributed in human organs and tissues. The activation of transcriptional and signaling cascades controls bile acid metabolism and synthesis, lipid and carbohydrate metabolism, immune cell expression, and inflammatory responses. A large body of evidence indicates that bile acids play an important role in the initiation and development of AS, and are strongly associated with AS risk factors. The major bile acid receptors, nuclear receptor farnesoid X receptor (liver) and membrane receptor G protein-coupled receptor 5, exhibit anti-atherosclerotic effects. Other nuclear receptors exert different anti-atherosclerotic or pro-atherosclerotic effects. In this review, we summarize the current knowledge on the effects of bile acids and their receptors in AS and explore the pathway of bile acids involved in atherosclerotic lesions. The main research based on animal models or cell/tissue culture experiments is also discussed. This review provides new ideas for the development of novel therapeutic approaches for AS prevention and treatment.

Zhengganxifeng Decoction Affects Gut Microbiota and Reduces Blood Pressure via Renin-Angiotensin System.

Zhengganxifeng decoction (ZGXFD) is a traditional Chinese medicinal formula, from "Medical Zhong parameter West recorded" by Xichun Zhang, which has been applied to the treatment of clinical essential hypertension. Besides its effect in blood pressure reduction, ZGXFD is also known to be a radical therapy with little or no side effects. Compared with western medicines, Chinese medicinal formulas have the advantage of simultaneously attacking multiple targets. However, such a property brings trouble to the pharmacological studies of Chinese medicines. This study investigated the composition of gut microbiota in spontaneously hypertensive rats (SHR) treated with ZGXFD. ZGXFD was shown to cause similar effects in the treatment group as benazepril: both were able to reduce in SHR the microbial diversity, Firmicutes to Bacteroidetes (F/B) ratio and coccus to bacillus (C/B) ratio. Meanwhile, ZGXFD can maintain the integrity of intestinal mechanistic barrier and elevate the percentage of bacteria producing short chain fatty acids (SCFA). By investigating renin-angiotensin system (RAS) system, we found that ZGXFD can decrease the expression of angiotensin-converting-enzyme (ACE) in lungs, which in turn causes a increase in AngI produces angiotensin1-7 (Ang1-7) and decrease in AngII. ZGXFD regulate blood pressure in SHR via RAS.

Effect of vitamin B2, vitamin C, vitamin D, vitamin E and folic acid in adults with essential hypertension: a systematic review and network meta-analysis.

OBJECTIVES: The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023. OUTCOMES: The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline. RESULTS: A total of 23 studies comparing five vitamins (vitamin B2, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: -14.14 mm Hg, 95% credible intervals: -27.62 to -0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins. CONCLUSIONS: According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding. PROSPERO REGISTRATION NUMBER: CRD42022352332.

Fecal Microbiota Transplantation Regulates Blood Pressure by Altering Gut Microbiota Composition and Intestinal Mucosal Barrier Function in Spontaneously Hypertensive Rats.

Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.