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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 -
Handbook of Experimental Pharmacology 2022Hypercholesterolemia is a major risk factor in atherosclerosis development and lipid-lowering drugs (i.e., statins) remain the treatment of choice. Despite effective... (Review)
Review
Hypercholesterolemia is a major risk factor in atherosclerosis development and lipid-lowering drugs (i.e., statins) remain the treatment of choice. Despite effective reduction of LDL cholesterol in patients, a residual cardiovascular risk persists in some individuals, highlighting the need for further therapeutic intervention. Recently, the CANTOS trial paved the way toward the development of specific therapies targeting inflammation, a key feature in atherosclerosis progression. The pre-existence of multiple drugs modulating both innate and adaptive immune responses has significantly accelerated the number of translational studies applying these drugs to atherosclerosis. Additional preclinical research has led to the discovery of new therapeutic targets, offering promising perspectives for the treatment and prevention of atherosclerosis. Currently, both drugs with selective targeting and broad unspecific anti-inflammatory effects have been tested. In this chapter, we aim to give an overview of current advances in immunomodulatory treatment approaches for atherosclerotic cardiovascular diseases.
Topics: Anti-Inflammatory Agents; Atherosclerosis; Clinical Trials as Topic; Humans; Hypercholesterolemia; Immunomodulation; Inflammation
PubMed: 34251531
DOI: 10.1007/164_2021_505 -
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 -
BioFactors (Oxford, England) Mar 2020A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL)... (Review)
Review
A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.
Topics: Aryldialkylphosphatase; Atherosclerosis; Humans
PubMed: 31400246
DOI: 10.1002/biof.1549 -
Advances in Experimental Medicine and... 2023Despite successive advancement of genome editing technology with zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the recent... (Review)
Review
Despite successive advancement of genome editing technology with zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the recent breakthrough in the field has been related to clustered regularly interspaced short palindromic repeats/associated proteins (CRISPR/Cas). The high efficiency and convenience of CRIPSR/Cas systems dramatically accelerate pre- and clinical experimentations of dyslipidemia and atherosclerosis. In this chapter, we review the latest state of genome editing in translational research of dyslipidemia and atherosclerosis. We highlight recent progress in therapeutic development for familial dyslipidemia by genome editing. We point to the challenges in maximizing efficacy and minimizing safety issues related to the once-and-done therapy focusing on CRISPR/Cas systems. We give an outlook on the potential gene targets prioritized by large-scale genetic studies of cardiovascular diseases and genome editing in precision medicine of dyslipidemia and atherosclerosis.
Topics: Humans; Gene Editing; Dyslipidemias; Atherosclerosis; Transcription Activator-Like Effector Nucleases; Cardiovascular Diseases
PubMed: 36454465
DOI: 10.1007/978-981-19-5642-3_10 -
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 -
Atherosclerosis Jan 2022
Topics: Arteriosclerosis; Atherosclerosis; Cardiovascular Diseases; Heart Disease Risk Factors; Humans; Lower Extremity; Risk Factors
PubMed: 34895917
DOI: 10.1016/j.atherosclerosis.2021.11.027 -
Immunotherapy Oct 2021Atherosclerosis, a chronic inflammatory condition in which atheroma accumulates within the intima of the arterial wall, is a life-threatening manifestation of... (Review)
Review
Atherosclerosis, a chronic inflammatory condition in which atheroma accumulates within the intima of the arterial wall, is a life-threatening manifestation of cardiovascular disease, due to atheroma rupture, chronic luminal narrowing and thrombosis. Current knowledge of the role of a protective immune response in atherosclerotic lesions has provided promising opportunities to develop new immunotherapeutic strategies. In particular, Tregs exert an atheroprotective role by releasing anti-inflammatory cytokines (IL-10/TGF-β) and suppressing autoreactive T lymphocytes. animal experiments have shown that this can be achieved by developing vaccines that stimulate immunological tolerance to atheroma antigens. Here, we present an overview of the current knowledge of the proatherogenic immune response, and we discuss the strategies currently used as immunoregulatory therapy.
Topics: Animals; Atherosclerosis; Humans; Immunotherapy
PubMed: 34382409
DOI: 10.2217/imt-2021-0009 -
Current Opinion in Lipidology Oct 2020Lipoproteins have significant role in both the promotion and prevention of atherosclerosis. This brief review will focus on recent reports on relationship between HDL... (Review)
Review
PURPOSE OF REVIEW
Lipoproteins have significant role in both the promotion and prevention of atherosclerosis. This brief review will focus on recent reports on relationship between HDL and HDL subclasses and their composition and function, the role of apoC-III in metabolism of triglyceride-rich lipoproteins, the impact of Lipoprotein (a) (Lp(a)) on endothelial cells, and the mechanism of uptake of aggregated LDL by macrophages.
RECENT FINDINGS
The complexity of the protein and lipid content of murine and human HDL and their relationship to its cholesterol efflux capacity have been examined. HDL has also been shown to have both antiatherogenic and proatherogenic properties. The relationship between apoC-III and LPL activity, apoprotein E mediated clearance of triglyceride-rich lipoproteins and the potential importance of apoC-III in the increased risk of cardiovascular disease in type 1 diabetics has been investigated. Oxidized phospholipid in Lp(a) promotes endothelial cells inflammatory and glycolytic responses. TLR4 participates in the uptake of aggregated LDL to contribute to foam cell formation.
SUMMARY
These studies contribute to our mechanistic understanding of how lipoproteins contribute to atherogenesis and identify potential therapeutic targets.
Topics: Animals; Atherosclerosis; Endothelial Cells; Humans; Lipoproteins
PubMed: 32773467
DOI: 10.1097/MOL.0000000000000704 -
Clinica Chimica Acta; International... Jun 2022Atherosclerosis (AS) is a chronic inflammatory lesion of the arterial vessel wall caused by a variety of complex factors. Furthermore, it is a major cause of... (Review)
Review
Atherosclerosis (AS) is a chronic inflammatory lesion of the arterial vessel wall caused by a variety of complex factors. Furthermore, it is a major cause of cardiovascular disease and a leading cause of death. Circular RNAs (circRNAs) are a new family of endogenous non-coding RNAs with unique covalently closed loops that have sparked interest due to their unique characteristics and potential diagnostic and therapeutic applications in various diseases. A growing number of studies have shown that circRNAs can be used as biomarkers for the diagnosis and treatment of AS. In this article, we review the biogenesis, classification as well as functions of circRNA and summarize the research on circRNA as a diagnostic biomarker for AS. Finally, we describe the regulatory capacity of circRNA in AS pathogenesis through its pathogenesis and demonstrate the potential therapeutic role of circRNA for AS.
Topics: Atherosclerosis; Biomarkers; Cardiovascular Diseases; Humans; MicroRNAs; RNA, Circular
PubMed: 35339453
DOI: 10.1016/j.cca.2022.03.016