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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 -
Clinica Chimica Acta; International... Aug 2019Extracellular vesicles (EVs), which exist in human blood, are increased in some inflammation-related cardiovascular diseases. EVs are involved in inflammation, immunity,... (Review)
Review
Extracellular vesicles (EVs), which exist in human blood, are increased in some inflammation-related cardiovascular diseases. EVs are involved in inflammation, immunity, signal transduction, cell survival and apoptosis, angiogenesis, thrombosis, and autophagy, all of which are highly significant for maintaining homeostasis and disease progression. Therefore, EVs are also associated with key steps in atherosclerosis, including cellular lipid metabolism, endothelial dysfunction and vascular wall inflammation, ultimately resulting in vascular remodelling. In this review, we summarize recent studies on EV contents and biological function, focusing on their potential effect in atherosclerosis, including cholesterol metabolism, vascular inflammation, angiogenesis, coagulation and the development of atherosclerotic lesions. EVs may represent potential biomarkers and pharmacological targets for atherosclerotic diseases.
Topics: Animals; Atherosclerosis; Extracellular Vesicles; Humans
PubMed: 30959044
DOI: 10.1016/j.cca.2019.04.051 -
Critical Pathways in Cardiology Sep 2019Several studies have gathered interest in the relationship between gut microbiota and atherosclerosis. Gut microbiota and its metabolites, such as... (Review)
Review
Several studies have gathered interest in the relationship between gut microbiota and atherosclerosis. Gut microbiota and its metabolites, such as trimethylamine-N-oxide, and gut dysbiosis play an important role in the development of atherosclerosis. Also, inflammation, derived by the intestinal tract, adds another mechanism through which the ecosystem of the human body affects the metabolic diseases and, furthermore, cardiovascular diseases. The scientific world should fixate the understanding of the exact physiologic and pathophysiologic mechanisms for atherogenesis by gut microbiota and through that, new ways for novel therapeutic targets will be available in the coming years. This review summarizes the latest data on this matter.
Topics: Atherosclerosis; Disease Management; Gastrointestinal Microbiome; Humans; Inflammation; Methylamines
PubMed: 31348074
DOI: 10.1097/HPC.0000000000000187 -
Artificial Cells, Nanomedicine, and... Dec 2019Atherosclerosis is a complex disease with involvement of intermediate-, large-sized arteries. Atherosclerosis is characterized by the accumulation of vascular lipids,... (Review)
Review
Atherosclerosis is a complex disease with involvement of intermediate-, large-sized arteries. Atherosclerosis is characterized by the accumulation of vascular lipids, immune system activation, inflammation, oxidative stress and oxidized low-density lipoproteins (LDLs), endothelial cell (EC) activation, arterial smooth muscle cell (SMC) proliferation, macrophage activation and foam cell formation that cause endothelial dysfunction. DNA methylation is one of important epigenetic mechanisms which changes gene expression. It has been evident that this mechanism plays an important role in the initiation and propagation of atherosclerosis. Furthermore, DNA methylation is a crucial and distinct mechanism that modulates genes governing cell proliferation, thereby connecting environmental insults with gene expression. This study represents many atherosclerosis-related genes which are regulated through DNA methylation mechanism. Although the role of epigenetics in atherosclerosis is at their infancy. Nevertheless, various studies demonstrated that DNA methylation involvement in this disease is undeniable. DNA methyltransferases are the main player of the smooth muscle cell proliferation, endothelial cell integrity, as well as arteriosclerosis formation. In this review, we focus on recent achievements in the functional and description interpretation of the DNA methylation pattern of cells and tissues implicated in atherosclerosis. Besides, we discuss the association of DNA methylation with oxidative stress, hyperhomocysteinemia (HHcy), ageing, and inflammation in the development and pathogenesis of atherosclerosis.
Topics: Aging; Animals; Atherosclerosis; DNA Methylation; Humans; Hyperhomocysteinemia; Myocytes, Smooth Muscle; Oxidative Stress
PubMed: 31116040
DOI: 10.1080/21691401.2019.1617724 -
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 -
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 -
International Journal of Molecular... Mar 2022Atherosclerosis is a chronic and progressive inflammatory disease of the arteries initiated by the functional and structural alteration of the endothelial layer...
Atherosclerosis is a chronic and progressive inflammatory disease of the arteries initiated by the functional and structural alteration of the endothelial layer responsible for promoting the subendothelial retention of modified low-density lipoproteins (LDL), which in turn generate an active proinflammatory state in which environmental factors, such as oxidizing agents, growth factors, cytokines, monocyte-macrophages and smooth muscle cells (SMCs), work in cooperation to promote the formation of plaque [...].
Topics: Atherosclerosis; Humans; Lipoproteins, LDL; Molecular Biology; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Plaque, Atherosclerotic
PubMed: 35408804
DOI: 10.3390/ijms23073444 -
Current Opinion in Lipidology Oct 2020Fibroblasts are very heterogeneous and plastic cells in the vasculature. A growing interest in fibroblasts in healthy and atherosclerotic vasculature is observed, next... (Review)
Review
PURPOSE OF REVIEW
Fibroblasts are very heterogeneous and plastic cells in the vasculature. A growing interest in fibroblasts in healthy and atherosclerotic vasculature is observed, next to macrophages, endothelial cells, and smooth muscle cells (SMCs). In this review, we discuss fibroblast presence, heterogeneity, origin, and plasticity in health and atherosclerosis based on latest literature.
RECENT FINDINGS
With help of single cell sequencing (SCS) techniques, we have gained more insight into presence and functions of fibroblasts in atherosclerosis. Next to SMCs, fibroblasts are extracellular matrix-producing cells abundant in the vasculature and involved in atherogenesis. Fibroblasts encompass a heterogeneous population and SCS data reveal several fibroblast clusters in healthy and atherosclerotic tissue with varying gene expression and function. Moreover, recent findings indicate interesting similarities between adventitial stem and/or progenitor cells and fibroblasts. Also, communication with inflammatory cells opens up a new therapeutic avenue.
SUMMARY
Because of their highly plastic and heterogeneous nature, modulating fibroblast cell function and communication in the atherosclerotic vessel might be useful in battling atherosclerosis from within the plaque.
Topics: Animals; Atherosclerosis; Cell Communication; Fibroblasts; Gene Expression Regulation; Humans
PubMed: 32773464
DOI: 10.1097/MOL.0000000000000700 -
Cell Communication and Signaling : CCS Nov 2023Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most... (Review)
Review
Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract.
Topics: Humans; DNA Methylation; Histones; Atherosclerosis; Plaque, Atherosclerotic; Epigenesis, Genetic; Protein Processing, Post-Translational; Inflammation
PubMed: 38031118
DOI: 10.1186/s12964-023-01298-8