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International Journal of Molecular... Apr 2023Polyphenols have attracted tremendous attention due to their pro-health properties, including their antioxidant, anti-inflammatory, antibacterial and neuroprotective... (Review)
Review
Polyphenols have attracted tremendous attention due to their pro-health properties, including their antioxidant, anti-inflammatory, antibacterial and neuroprotective activities. Atherosclerosis is a vascular disorder underlying several CVDs. One of the main risk factors causing atherosclerosis is the type and quality of food consumed. Therefore, polyphenols represent promising agents in the prevention and treatment of atherosclerosis, as demonstrated by in vitro, animal, preclinical and clinical studies. However, most polyphenols cannot be absorbed directly by the small intestine. Gut microbiota play a crucial role in converting dietary polyphenols into absorbable bioactive substances. An increasing understanding of the field has confirmed that specific GM taxa strains mediate the gut microbiota-atherosclerosis axis. The present study explores the anti-atherosclerotic properties and associated underlying mechanisms of polyphenols. Moreover, it provides a basis for better understanding the relationship between dietary polyphenols, gut microbiota, and cardiovascular benefits.
Topics: Animals; Polyphenols; Gastrointestinal Microbiome; Risk Factors; Anti-Inflammatory Agents; Atherosclerosis
PubMed: 37108307
DOI: 10.3390/ijms24087146 -
Arteriosclerosis, Thrombosis, and... Mar 2015Mechanistic studies over the past decades using in vitro systems, animal models, and human tissues have highlighted the complexity of pathophysiological processes of... (Review)
Review
Mechanistic studies over the past decades using in vitro systems, animal models, and human tissues have highlighted the complexity of pathophysiological processes of atherosclerosis. Hypercholesterolemia, as one of the major risk factors for the development and progression of atherosclerosis, is still the focus of many mechanistic studies and the major therapeutic target of atherosclerosis. Although there is a dire need to validate many experimental findings in humans, there is a large number of approaches that have been showing promise for contributing to future therapeutic strategies.
Topics: Animals; Arteries; Atherosclerosis; Disease Models, Animal; Humans; Inflammation Mediators; Lipids; Lipoproteins; Signal Transduction
PubMed: 25717174
DOI: 10.1161/ATVBAHA.115.305380 -
Indian Heart Journal Mar 2024Lp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or... (Review)
Review
Lp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or >125 nmol/L) whereas in Indians it is 25 %. Epidemiological, genome-wide association and mendelian randomization studies have demonstrated an association between elevated Lp(a) levels and increased incidence of myocardial infarction, aortic valve stenosis, ischemic stroke, heart failure, CV and all-cause mortality. The increased Lp(a)-mediated CV risk is mediated by pro-inflammatory, pro-thrombotic and pro-atherogenic processes, leading to progression of atherosclerosis and increased risk of thrombosis. Lp(a) level reaches peak by 5 years of age and remains stable over time. Levels are not much influenced by dietary and environmental factors but it can vary in certain clinical situations like thyroid diseases, chronic kidney disease, inflammation and sepsis. It should be measured at least once in life time. Cascade testing for high Lp(a) is recommended in the settings of FH, family history of (very) high Lp(a), and personal or family history of ASCVD. In the absence of specific Lp(a)-lowering therapies, comprehensive risk factor management is recommended as per guidelines for individuals with elevated Lp(a). PCSK9 inhibitors and Inclisiran reduce Lp(a) by 25%. Pelacarsen is an antisense oligonucleotide and is found to reduce Lp(a) by 80%. In a recent Indian study of 1,021 CAD patients, presence of elevated Lp(a) (>50 mg/dL) correlated with severe angiographic disease. 37% of ACS patients exhibited elevated Lp(a) and it was higher in young CAD patients with FH (43%).
Topics: Humans; Proprotein Convertase 9; Lipoprotein(a); Genome-Wide Association Study; Risk Factors; Atherosclerosis; Hyperlipidemias
PubMed: 38160790
DOI: 10.1016/j.ihj.2023.12.010 -
Journal of the American College of... Dec 2014Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and... (Review)
Review
Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and exogenous antigens. Both proatherogenic as well as atheroprotective roles have been identified for the immune system in atherosclerosis. Hence, it is conceivable that an immunomodulatory strategy via active immunization against many of these antigens could potentially alter the natural history of atherosclerosis. This review discusses: 1) the complex role of important components of the innate and adaptive immune systems in atherogenesis; 2) the nature of many antigens that have been tested successfully in vaccine formulations to reduce atherosclerosis in pre-clinical experimental models; and 3) the potential opportunities and challenges for clinical application of vaccination for atherosclerosis in the future.
Topics: Adaptive Immunity; Atherosclerosis; Humans; Immunity, Innate; Vaccines
PubMed: 25541132
DOI: 10.1016/j.jacc.2014.10.018 -
Trends in Pharmacological Sciences Apr 2019Atherosclerosis is the primary underlying cause of cardiovascular disease which preferentially develops at arterial regions exposed to disturbed flow (DF), but much less... (Review)
Review
Atherosclerosis is the primary underlying cause of cardiovascular disease which preferentially develops at arterial regions exposed to disturbed flow (DF), but much less at regions of unidirectional laminar flow (UF). Recent studies have demonstrated that DF and UF differentially regulate important aspects of endothelial function, such as vascular inflammation, oxidative stress, vascular tone, cell proliferation, senescence, mitochondrial function, and glucose metabolism. DF and UF regulate vascular pathophysiology via differential regulation of mechanosensitive transcription factors (MSTFs) (KLF2, KLF4, NRF2, YAP/TAZ/TEAD, HIF-1α, NF-κB, AP-1, and others). Emerging studies show that MSTFs represent promising therapeutic targets for the prevention and treatment of atherosclerosis. We present here a comprehensive overview of the role of MSTFs in atherosclerosis, and highlight future directions for developing novel therapeutic agents by targeting MSTFs.
Topics: Animals; Atherosclerosis; Drug Development; Humans; Kruppel-Like Factor 4; Mechanotransduction, Cellular; Molecular Targeted Therapy; Transcription Factors
PubMed: 30826122
DOI: 10.1016/j.tips.2019.02.004 -
Hamostaseologie Dec 2021Atherosclerotic vascular disease and its related complications are the major cause of mortality in Western societies. Atherosclerosis is a chronic inflammatory disease... (Review)
Review
Atherosclerotic vascular disease and its related complications are the major cause of mortality in Western societies. Atherosclerosis is a chronic inflammatory disease of the arterial wall triggered by traditional and nontraditional risk factors and mediated by inflammatory and immune responses. Recent clinical trials provided compelling evidence corroborating that atherosclerosis is an inflammatory disease and demonstrated efficacy of anti-inflammatory interventions in reducing cardiovascular events and mortality. Traditional risk factors drive vascular inflammation, further justifying the instrumental role of intensified risk factor management in attenuating and preventing atherosclerotic disease and complications. Promising therapeutic approaches specifically related to inhibition of inflammation span traditional anti-inflammatory drugs, specific immunomodulation, and development of vaccination against atherosclerotic disease. Here, we review the inflammatory component in atherogenesis, the available evidence from clinical trials evaluating efficacy of therapeutic anti-inflammatory interventions in patients with high cardiovascular risk, and discuss potential future targets for anti-inflammatory or immune modulatory treatment in atherosclerotic cardiovascular disease.
Topics: Anti-Inflammatory Agents; Arteries; Atherosclerosis; Humans; Immunomodulation; Inflammation
PubMed: 34942656
DOI: 10.1055/a-1661-0020 -
The Canadian Journal of Cardiology Mar 2017MicroRNAs are short noncoding RNAs, expressed in humans and involved in sequence-specific post-transcriptional regulation of gene expression. They have emerged as key... (Review)
Review
MicroRNAs are short noncoding RNAs, expressed in humans and involved in sequence-specific post-transcriptional regulation of gene expression. They have emerged as key players in a wide array of biological processes, and changes in their expression and/or function have been associated with plethora of human diseases. Atherosclerosis and its related clinical complications, such as myocardial infarction or stroke, represent the leading cause of death in the Western world. Accumulating experimental evidence has revealed a key role for microRNAs in regulating cellular and molecular processes related to atherosclerosis development, ranging from risk factors, to plaque initiation and progression, up to atherosclerotic plaque rupture. In this review, we focus on how microRNAs can influence atherosclerosis biology, as well as the potential clinical applications of microRNAs, which are being developed as targets as well as therapeutic agents for a growing industry hoping to harness the power of RNA-guided gene regulation to fight disease and infection.
Topics: Atherosclerosis; Disease Progression; Gene Expression Regulation; Genetic Therapy; Humans; MicroRNAs
PubMed: 28232017
DOI: 10.1016/j.cjca.2017.01.001 -
Bioscience Reports Jul 2022An estimated 97% of the human genome consists of non-protein-coding sequences. As our understanding of genome regulation improves, this has led to the characterization... (Review)
Review
An estimated 97% of the human genome consists of non-protein-coding sequences. As our understanding of genome regulation improves, this has led to the characterization of a diverse array of non-coding RNAs (ncRNA). Among these, micro-RNAs (miRNAs) belong to the short ncRNA class (22-25 nucleotides in length), with approximately 2500 miRNA genes encoded within the human genome. From a therapeutic perspective, there is interest in exploiting miRNA as biomarkers of disease progression and response to treatments, as well as miRNA mimics/repressors as novel medicines. miRNA have emerged as an important class of RNA master regulators with important roles identified in the pathogenesis of atherosclerotic cardiovascular disease. Atherosclerosis is characterized by a chronic inflammatory build-up, driven largely by low-density lipoprotein cholesterol accumulation within the artery wall and vascular injury, including endothelial dysfunction, leukocyte recruitment and vascular remodelling. Conventional therapy focuses on lifestyle interventions, blood pressure-lowering medications, high-intensity statin therapy and antiplatelet agents. However, a significant proportion of patients remain at increased risk of cardiovascular disease. This continued cardiovascular risk is referred to as residual risk. Hence, a new drug class targeting atherosclerosis could synergise with existing therapies to optimise outcomes. Here, we review our current understanding of the role of ncRNA, with a focus on miRNA, in the development and progression of atherosclerosis, highlighting novel biological mechanisms and therapeutic avenues.
Topics: Atherosclerosis; Biomarkers; Cardiovascular Diseases; Humans; MicroRNAs; RNA, Untranslated
PubMed: 35758143
DOI: 10.1042/BSR20212355 -
Current Atherosclerosis Reports Jun 2021Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind... (Review)
Review
PURPOSE OF REVIEW
Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind cardiovascular diseases (CVD), such as coronary artery disease, peripheral artery disease, and stroke. In this review, we discuss and describe novel RNA interference (RNAi)-based therapies in clinical trials and on the market.
RECENT FINDINGS
The first RNAi-based therapies have entered clinical use for the control of atherosclerosis risk factors, i.e., blood cholesterol levels. The most advanced treatment is silencing of proprotein convertase subtilisin/kexin type 9 (PCSK9) with a drug called inclisiran, which has been approved for the treatment of hypercholesterolemia in late 2020, and results in a robust decrease in plasma cholesterol levels. As the new RNAi therapies for atherosclerosis are now entering markets, the usefulness of these therapies will be further evaluated in larger patient cohorts. Thus, it remains to be seen how fast, effectively and eminently these new drugs consolidate their niche within the cardiovascular disease drug palette.
Topics: Atherosclerosis; Humans; Hypercholesterolemia; Proprotein Convertase 9; RNAi Therapeutics
PubMed: 34146172
DOI: 10.1007/s11883-021-00938-z -
Clinical Science (London, England :... May 2021Atherosclerosis is a disease of large and medium arteries that can lead to life-threatening cerebrovascular and cardiovascular consequences such as heart failure and... (Review)
Review
Atherosclerosis is a disease of large and medium arteries that can lead to life-threatening cerebrovascular and cardiovascular consequences such as heart failure and stroke and is a major contributor to cardiovascular-related mortality worldwide. Atherosclerosis development is a complex process that involves specific structural, functional and transcriptional changes in different vascular cell populations at different stages of the disease. The application of single-cell RNA sequencing (scRNA-seq) analysis has discovered not only disease-related cell-specific transcriptomic profiles but also novel subpopulations of cells once thought as homogenous cell populations. Vascular cells undergo specific transcriptional changes during the entire course of the disease. Epigenetics is the instruction-set-architecture in living cells that defines and maintains the cellular identity by regulating the cellular transcriptome. Although different cells contain the same genetic material, they have different epigenomic signatures. The epigenome is plastic, dynamic and highly responsive to environmental stimuli. Modifications to the epigenome are driven by an array of epigenetic enzymes generally referred to as writers, erasers and readers that define cellular fate and destiny. The reversibility of these modifications raises hope for finding novel therapeutic targets for modifiable pathological conditions including atherosclerosis where the involvement of epigenetics is increasingly appreciated. This article provides a critical review of the up-to-date research in the field of epigenetics mainly focusing on in vivo settings in the context of the cellular role of individual vascular cell types in the development of atherosclerosis.
Topics: Animals; Atherosclerosis; DNA Methylation; Endothelial Cells; Epigenesis, Genetic; Fibroblasts; Histone Code; Humans; Lymphocytes; Macrophages; Molecular Targeted Therapy; Myocytes, Smooth Muscle; Plaque, Atherosclerotic; Single-Cell Analysis
PubMed: 33988232
DOI: 10.1042/CS20201066