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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 -
BMC Biology Feb 2023Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the...
BACKGROUND
Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study.
RESULTS
Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8 T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4 CD28 T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2SPP1 foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses.
CONCLUSIONS
We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies.
Topics: Humans; Atherosclerosis; Biological Transport; CD8-Positive T-Lymphocytes; Immunotherapy
PubMed: 36855107
DOI: 10.1186/s12915-023-01540-2 -
Archives of Cardiovascular Diseases Dec 2016Atherosclerosis is an inflammatory disease within the arterial wall that is responsible for several important adverse vascular events, including coronary artery disease,... (Review)
Review
Atherosclerosis is an inflammatory disease within the arterial wall that is responsible for several important adverse vascular events, including coronary artery disease, myocardial infraction, stroke and peripheral artery disease. Both innate and adaptive immunity play important roles in the development of atherosclerosis. In particular, monocytes/macrophages, which are the surrogate cells of innate immunity, have important proatherogenic effects. In addition, adaptive immune responses effected by T cells play important roles in atherosclerosis. While the T-helper cell type 1 (Th1) response has a potent proatherogenic effect, the pathogenic roles of other T cell subsets, such as the Th2 and Th17 pathways, remain controversial. However, the antiatherosclerotic protective roles of regulatory T cells and some Th2-related cytokines, such as interleukin-5, have been clearly established. In light of numerous data in animal models showing the importance of inflammatory cells in atherosclerosis and its complications, treatment of cardiovascular diseases with anti-inflammatory drugs may be an attractive strategy. However, future randomized placebo-controlled trials are required to test this possibility, to evaluate the proper effect of anti-inflammatory drugs as cardiovascular therapeutic agents without confounding effects.
Topics: Adaptive Immunity; Animals; Atherosclerosis; Humans; Inflammation; Inflammation Mediators
PubMed: 27595467
DOI: 10.1016/j.acvd.2016.04.002 -
Advanced Science (Weinheim,... Dec 2023With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death.... (Review)
Review
With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death. Due to their fascinating physical, chemical, and biological characteristics, nanomaterials are regarded as a promising tool to tackle enormous challenges in medicine. The emerging discipline of nanomedicine has filled a huge application gap in the atherosclerotic field, ushering a new generation of diagnosis and treatment strategies. Herein, based on the essential pathogenic contributors of atherogenesis, as well as the distinct composition/structural characteristics, synthesis strategies, and surface design of nanoplatforms, the three major application branches (nanodiagnosis, nanotherapy, and nanotheranostic) of nanomedicine in atherosclerosis are elaborated. Then, state-of-art studies containing a sequence of representative and significant achievements are summarized in detail with an emphasis on the intrinsic interaction/relationship between nanomedicines and atherosclerosis. Particularly, attention is paid to the biosafety of nanomedicines, which aims to pave the way for future clinical translation of this burgeoning field. Finally, this comprehensive review is concluded by proposing unresolved key scientific issues and sharing the vision and expectation for the future, fully elucidating the closed loop from atherogenesis to the application paradigm of nanomedicines for advancing the early achievement of clinical applications.
Topics: Humans; Nanomedicine; Atherosclerosis; Nanostructures
PubMed: 37897322
DOI: 10.1002/advs.202304294 -
Vascular Health and Risk Management 2023Multiple lines of evidence confirm that the cumulative burden of low-density lipoprotein cholesterol (LDL-C) is causally related to the development of atherosclerotic... (Review)
Review
Multiple lines of evidence confirm that the cumulative burden of low-density lipoprotein cholesterol (LDL-C) is causally related to the development of atherosclerotic cardiovascular disease (ASCVD). As such, lowering LDL-C is a central tenet in all ASCVD prevention guidelines, which recommend matching the intensity of LDL-C lowering with the absolute risk of the patient. Unfortunately, issues such as difficulty with long-term adherence to statin therapy and inability to achieve desired LDL-C thresholds with statins alone results in residual elevated ASCVD risk. Non-statin therapies generally provide similar risk reduction per mmol/L of LDL-C reduction and are included by major society guidelines as part of the treatment algorithm for managing LDL-C. Per the 2022 American College of Cardiology Expert Consensus Decision Pathway, patients with ASCVD are recommended to achieve both an LDL-C reduction ≥50% and an LDL-C threshold of <55 mg/dL in patients at very high-risk and <70 mg/dL in those not at very high risk. Patients with familial hypercholesterolemia (FH) but without ASCVD should lower LDL-C to <100 mg/dL. For patients who remain above LDL-C thresholds with maximally tolerated statin therapy plus lifestyle changes, non-statin therapy warrants strong consideration. While several non-statin therapies have been granted FDA approval for managing hypercholesterolemia (eg, ezetimibe, Proprotein Convertase Subtilisin/Kexin 9 [PCSK9] monoclonal antibodies, and bempedoic acid), the focus of the current review is on inclisiran, a novel small interfering RNA therapy that inhibits the production of the PCSK9 protein. Inclisiran is currently FDA approved as an adjunct to statin therapy in patients with clinical ASCVD or heterozygous FH who require additional LDL-lowering. The drug is administered by subcutaneous injection twice a year, after an initial baseline and 3 month dose. In this review, we sought to provide an overview of the use of inclisiran, review current trial data, and outline an approach to potential patient selection.
Topics: Humans; Proprotein Convertase 9; Cholesterol, LDL; Cardiovascular Diseases; RNA, Small Interfering; Atherosclerosis; Hyperlipoproteinemia Type II
PubMed: 37434791
DOI: 10.2147/VHRM.S338424 -
Arteriosclerosis, Thrombosis, and... Apr 2020The immune system's role in atherosclerosis has long been an important research topic and is increasingly investigated for therapeutic and diagnostic purposes.... (Review)
Review
The immune system's role in atherosclerosis has long been an important research topic and is increasingly investigated for therapeutic and diagnostic purposes. Therefore, noninvasive imaging of hematopoietic organs and immune cells will undoubtedly improve atherosclerosis phenotyping and serve as a monitoring method for immunotherapeutic treatments. Among the available imaging techniques, positron emission tomography's unique features make it an ideal tool to quantitatively image the immune response in the context of atherosclerosis and afford reliable readouts to guide medical interventions in cardiovascular disease. Here, we summarize the state of the art in the field of atherosclerosis positron emission tomography immunoimaging and provide an outlook on current and future applications.
Topics: Atherosclerosis; Hematopoietic System; Humans; Nanoparticles; Phagocytes; Plaque, Atherosclerotic; Positron-Emission Tomography; Radioimmunodetection; Radiopharmaceuticals
PubMed: 32078338
DOI: 10.1161/ATVBAHA.119.313455 -
European Journal of Vascular and... Apr 2006The aim of this article is to discuss the role of inflammation in atherosclerosis. (Review)
Review
PURPOSE
The aim of this article is to discuss the role of inflammation in atherosclerosis.
SUMMARY
An initial chemical, mechanical or immunological insult induces endothelial dysfunction. This triggers a cascade of inflammatory reactions, in which monocytes, macrophages, T lymphocytes and vascular smooth muscle cells participate. Leukocyte adhesion molecules, cytokines, growth factors and metalloproteinases participate in all stages of atherogenesis. Almost all of the traditional risk factors for atherosclerosis are associated with and participate in the inflammatory process. Many infectious agents, mainly Chlamydia pneumoniae, have been proposed as potential triggers of the cascade. The immune system has been implicated in plaque formation, through the activation of cellular and humoral immunity against innate or microbial heat shock protein 60. Methods of detection of systemic or local plaque inflammation have been developed and research is being conducted on the potential use of anti-inflammatory and antibiotic drugs in atherosclerosis.
Topics: Atherosclerosis; Bacterial Infections; Endothelium, Vascular; Humans; Inflammation; Risk Factors
PubMed: 16359887
DOI: 10.1016/j.ejvs.2005.11.001 -
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 -
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 -
Current Opinion in Lipidology Oct 2018The immune system plays a critical role in the development and modulation of atherosclerosis. New high-parameter technologies, including mass cytometry (CyTOF) and... (Review)
Review
PURPOSE OF REVIEW
The immune system plays a critical role in the development and modulation of atherosclerosis. New high-parameter technologies, including mass cytometry (CyTOF) and single-cell RNA sequencing (scRNAseq), allow for an encompassing analysis of immune cells. Unexplored marker combinations and transcriptomes can define new immune cell subsets and suggest their functions. Here, we review recent advances describing the immune cells in the artery wall of mice with and without atherosclerosis. We compare technologies and discuss limitations and advantages.
RECENT FINDINGS
Both CyTOF and scRNAseq on leukocytes from digested aortae show 10-30 immune cell subsets. Myeloid, T, B and natural killer cells were confirmed. Although cellular functions can be inferred from RNA-Seq data, some subsets cannot be identified based on current knowledge, suggesting they may be new cell types. CyTOF and scRNAseq each identified four B-cell subsets and three macrophage subsets in the atherosclerotic aorta. Limitations include cell death caused by enzymatic digestion and the limited depth of the scRNAseq transcriptomes.
SUMMARY
High-parameter methods are powerful tools for uncovering leukocyte diversity. CyTOF is currently more powerful at discerning leukocyte subsets in the atherosclerotic aorta, whereas scRNAseq provides more insight into their likely functions.
Topics: Animals; Atherosclerosis; Humans; Prognosis; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 30020199
DOI: 10.1097/MOL.0000000000000537