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Signal Transduction and Targeted Therapy Jul 2022Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO...
Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR's metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P < 0.05; *P < 0.05), and 37 and 35% in plasma (***P < 0.001; *P < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.
Topics: Animals; Atherosclerosis; Choline; Cricetinae; Gastrointestinal Microbiome; Methylamines; Vitamins
PubMed: 35794102
DOI: 10.1038/s41392-022-01027-6 -
Circulation Research Jan 2021Atherosclerotic cardiovascular disease (ASCVD) proceeds through a series of stages: initiation, progression (or regression), and complications. By integrating known... (Review)
Review
Atherosclerotic cardiovascular disease (ASCVD) proceeds through a series of stages: initiation, progression (or regression), and complications. By integrating known biology regarding molecular signatures of each stage with recent advances in high-dimensional molecular data acquisition platforms (to assay the genome, epigenome, transcriptome, proteome, metabolome, and gut microbiome), snapshots of each phase of atherosclerotic cardiovascular disease development can be captured. In this review, we will summarize emerging approaches for assessment of atherosclerotic cardiovascular disease risk in humans using peripheral blood molecular signatures and molecular imaging approaches. We will then discuss the potential (and challenges) for these snapshots to be integrated into a personalized movie providing dynamic readouts of an individual's atherosclerotic cardiovascular disease risk status throughout the life course.
Topics: Animals; Atherosclerosis; Bacteria; Biomarkers; Disease Progression; Gastrointestinal Microbiome; Gene Expression Profiling; Heart Disease Risk Factors; Humans; Metabolome; Metabolomics; Molecular Imaging; Plaque, Atherosclerotic; Predictive Value of Tests; Proteome; Proteomics; Risk Assessment; Transcriptome
PubMed: 33476202
DOI: 10.1161/CIRCRESAHA.120.315890 -
Journal of the American College of... Jun 2021The MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute-sponsored prospective study aimed at studying the prevalence,... (Review)
Review
The MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute-sponsored prospective study aimed at studying the prevalence, progression, determinants, and prognostic significance of subclinical cardiovascular disease in a sex-balanced, multiethnic, community-dwelling U.S. cohort. MESA helped usher in an era of noninvasive evaluation of subclinical atherosclerosis presence, burden, and progression for the evaluation of atherosclerotic cardiovascular disease risk, beyond what could be predicted by traditional risk factors alone. Concepts developed in MESA have informed international patient care guidelines, providing new tools to effectively guide public health policy, population screening, and clinical decision-making. MESA is grounded in an open science model that continues to be a beacon for collaborative science. In this review, we detail the original goals of MESA, and describe how the scope of MESA has evolved over time. We highlight 10 significant MESA contributions to cardiovascular medicine, and chart the path forward for MESA in the year 2021 and beyond.
Topics: Atherosclerosis; Cardiac Imaging Techniques; Heart Disease Risk Factors; Humans; Lipoprotein(a); Prospective Studies; Vascular Calcification
PubMed: 34167645
DOI: 10.1016/j.jacc.2021.05.006 -
International Journal of Molecular... Apr 2022Long-term consequences of atherosclerosis remain the major culprit of mortality in developed and developing countries [...].
Long-term consequences of atherosclerosis remain the major culprit of mortality in developed and developing countries [...].
Topics: Atherosclerosis; Cardiovascular Diseases; Humans
PubMed: 35563086
DOI: 10.3390/ijms23094695 -
Circulation Research Apr 2020Technological advances in characterizing molecular heterogeneity at the single cell level have ushered in a deeper understanding of the biological diversity of cells... (Review)
Review
Technological advances in characterizing molecular heterogeneity at the single cell level have ushered in a deeper understanding of the biological diversity of cells present in tissues including atherosclerotic plaques. New subsets of cells have been discovered among cell types previously considered homogenous. The commercial availability of systems to obtain transcriptomes and matching surface phenotypes from thousands of single cells is rapidly changing our understanding of cell types and lineage identity. Emerging methods to infer cellular functions are beginning to shed new light on the interplay of components involved in multifaceted disease responses, like atherosclerosis. Here, we provide a technical guide for design, implementation, assembly, and interpretations of current single cell transcriptomics approaches from the perspective of employing these tools for advancing cardiovascular disease research.
Topics: Animals; Atherosclerosis; Biomedical Research; Gene Expression Profiling; Humans; RNA-Seq; Single-Cell Analysis; Transcriptome
PubMed: 32324494
DOI: 10.1161/CIRCRESAHA.119.315940 -
Nutrients Feb 2020The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease... (Review)
Review
The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.
Topics: Animals; Atherosclerosis; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Molecular Targeted Therapy; Precision Medicine; Probiotics
PubMed: 32110880
DOI: 10.3390/nu12030605 -
Arquivos Brasileiros de Cardiologia Jul 2017
Topics: Atherosclerosis; Biomarkers; Brazil; Dyslipidemias; Humans
PubMed: 28813069
DOI: 10.5935/abc.20170121 -
Journal of the American College of... Mar 2022There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians... (Review)
Review
There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in the 20- to 39-year age range (young adults). These include tobacco use, elevated blood pressure/hypertension, family history of premature ASCVD, primary severe hypercholesterolemia such as familial hypercholesterolemia, diabetes with diabetes-specific risk-enhancing factors, or the presence of multiple other risk-enhancing factors, including in females, a history of pre-eclampsia or menopause under age 40. The authors update current thinking on lipid risk factors such as triglycerides, non-high-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein (a) that are useful in understanding an individual's long-term ASCVD risk. The authors review emerging strategies, such as coronary artery calcium and polygenic risk scores in this age group, that have potential clinical utility, but whose best use remains uncertain. Finally, the authors discuss both the obstacles and opportunities for addressing prevention in early adulthood.
Topics: Atherosclerosis; Heart Disease Risk Factors; Humans; Risk Factors; Young Adult
PubMed: 35210038
DOI: 10.1016/j.jacc.2021.12.016 -
Atherosclerosis Jun 2023In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal... (Review)
Review
In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal association with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. One of the novelties of this statement is a new risk calculator showing how Lp(a) influences lifetime risk for ASCVD and that global risk may be underestimated substantially in individuals with high or very high Lp(a) concentration. The statement also provides practical advice on how knowledge about Lp(a) concentration can be used to modulate risk factor management, given that specific and highly effective mRNA-targeted Lp(a)-lowering therapies are still in clinical development. This advice counters the attitude: "Why should I measure Lp(a) if I can't lower it?". Subsequent to publication, questions have arisen relating to how the recommendations of this statement impact everyday clinical practice and ASCVD management. This review addresses 30 of the most frequently asked questions about Lp(a) epidemiology, its contribution to cardiovascular risk, Lp(a) measurement, risk factor management and existing therapeutic options.
Topics: Humans; Lipoprotein(a); Risk Factors; Risk Assessment; Aortic Valve Stenosis; Atherosclerosis; Cardiovascular Diseases
PubMed: 37188555
DOI: 10.1016/j.atherosclerosis.2023.04.012 -
Arteriosclerosis, Thrombosis, and... Jan 2021Lp(a) (lipoprotein[a]) concentrations are associated with atherosclerotic cardiovascular disease (ASCVD), and new therapies that enable potent and specific reduction are... (Observational Study)
Observational Study
OBJECTIVE
Lp(a) (lipoprotein[a]) concentrations are associated with atherosclerotic cardiovascular disease (ASCVD), and new therapies that enable potent and specific reduction are in development. In the largest study conducted to date, we address 3 areas of uncertainty: (1) the magnitude and shape of ASCVD risk conferred across the distribution of lipoprotein(a) concentrations; (2) variation of risk across racial and clinical subgroups; (3) clinical importance of a high lipoprotein(a) threshold to guide therapy. Approach and Results: Relationship of lipoprotein(a) to incident ASCVD was studied in 460 506 middle-aged UK Biobank participants. Over a median follow-up of 11.2 years, incident ASCVD occurred in 22 401 (4.9%) participants. Median lipoprotein(a) concentration was 19.6 nmol/L (25th-75th percentile 7.6-74.8). The relationship between lipoprotein(a) and ASCVD appeared linear across the distribution, with a hazard ratio of 1.11 (95% CI, 1.10-1.12) per 50 nmol/L increment. Substantial differences in concentrations were noted according to race-median values for white, South Asian, black, and Chinese individuals were 19, 31, 75, and 16 nmol/L, respectively. However, risk per 50 nmol/L appeared similar-hazard ratios of 1.11, 1.10, and 1.07 for white, South Asian, and black individuals, respectively. A high lipoprotein(a) concentration defined as ≥150 nmol/L was present in 12.2% of those without and 20.3% of those with preexisting ASCVD and associated with hazard ratios of 1.50 (95% CI, 1.44-1.56) and 1.16 (95% CI, 1.05-1.27), respectively.
CONCLUSIONS
Lipoprotein(a) concentrations predict incident ASCVD among middle-aged adults within primary and secondary prevention contexts, with a linear risk gradient across the distribution. Concentrations are variable across racial subgroups, but the associated risk appears similar.
Topics: Adult; Aged; Atherosclerosis; Biological Specimen Banks; Biomarkers; Female; Heart Disease Risk Factors; Humans; Incidence; Lipoprotein(a); Male; Middle Aged; Primary Prevention; Prognosis; Race Factors; Risk Assessment; Secondary Prevention; Time Factors; United Kingdom
PubMed: 33115266
DOI: 10.1161/ATVBAHA.120.315291