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Molecular Therapy : the Journal of the... Oct 2022Atherosclerosis is the main underlying pathology for many cardiovascular diseases (CVDs), which are the leading cause of death globally and represent a serious health... (Review)
Review
Atherosclerosis is the main underlying pathology for many cardiovascular diseases (CVDs), which are the leading cause of death globally and represent a serious health crisis. Atherosclerosis is a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease. Elevated plasma lipids, hypertension, and high glucose are the major risk factors for developing atherosclerotic plaques. To date, most pharmacological therapies aim to control these risk factors, but they do not target the plaque-causing cells themselves. In patients with acute coronary syndromes, surgical revascularization with percutaneous coronary intervention has greatly reduced mortality rates. However, stent thrombosis and neo-atherosclerosis have emerged as major safety concerns of drug eluting stents due to delayed re-endothelialization. This review summarizes the major milestones, strengths, and limitations of current anti-atherosclerotic therapies. It provides an overview of the recent discoveries and emerging game-changing technologies in the fields of nanomedicine, mRNA therapeutics, and gene editing that have the potential to revolutionize CVD clinical practice by steering it toward precision medicine.
Topics: Atherosclerosis; Drug-Eluting Stents; Glucose; Humans; Lipids; RNA, Messenger; Risk Factors; Treatment Outcome
PubMed: 36065464
DOI: 10.1016/j.ymthe.2022.08.024 -
Biological Trace Element Research Jul 2020Today atherosclerosis is considered as a main cause of death in the worldwide. There is a significant association between heavy metal exposure and atherosclerosis. In... (Review)
Review
Today atherosclerosis is considered as a main cause of death in the worldwide. There is a significant association between heavy metal exposure and atherosclerosis. In this study, we discussed the scientific literature about the effect of mercury on the pathogenesis of atherosclerosis. We also considered the epidemiological studies on mercury as a risk factor for atherosclerosis. Web of Science, Google Scholar, Medline, PubMed, and Scopus were searched by using the following keywords to 2019: (cardiovascular diseases OR atherosclerosis OR endothelial dysfunction) AND (mercury). Mercury has the potential to act as one of the novel risk factors for atherosclerosis development. The findings have indicated the role of mercury in the pathogenesis of atherosclerosis, vascular endothelial dysfunction, oxidative stress, inflammation, and dyslipidemia. Mercury can induce atherosclerosis indirectly via increasing the total cholesterol, triglycerides, and LDL-C levels as well as decreasing the HDL-C level. Mercury can be considered as a risk factor in the atherosclerosis progression. However, more studies are required to find the exact mechanisms involved in the pathogenesis of atherosclerosis induced by mercury.
Topics: Atherosclerosis; Cell Biology; Epidemiologic Studies; Humans; Mercury
PubMed: 31529242
DOI: 10.1007/s12011-019-01899-w -
Progress in Cardiovascular Diseases 2024Lipoprotein(a) [Lp(a)], a genetically determined macromolecular complex, is independently and causally associated with atherosclerotic cardiovascular disease (ASCVD) and... (Review)
Review
Lipoprotein(a) [Lp(a)], a genetically determined macromolecular complex, is independently and causally associated with atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis via proposed proinflammatory, prothrombotic, and proatherogenic mechanisms. While Lp(a) measurement standardization issues are being resolved, several guidelines now support testing Lp(a) at least once in each adult's lifetime for ASCVD risk prediction which can foster implementation of more aggressive primary or secondary prevention therapies. Currently, there are several emerging targeted Lp(a) lowering therapies in active clinical investigation for safety and cardiovascular benefit among both primary and secondary prevention populations. First degree relatives of patients with high Lp(a) should be encouraged to undergo cascade screening. Primary prevention patients with high Lp(a) should consider obtaining a coronary calcium score for further risk estimation and to guide further ASCVD risk factor management including consideration of low dose aspirin therapy. Secondary prevention patients with high Lp(a) levels should consider adding PCSK9 inhibition to statin therapy.
Topics: Humans; Lipoprotein(a); Biomarkers; Risk Assessment; Atherosclerosis; Risk Factors; Secondary Prevention; Heart Disease Risk Factors
PubMed: 38759878
DOI: 10.1016/j.pcad.2024.05.007 -
JCI Insight Sep 2022Cardiovascular diseases, especially atherosclerosis and its complications, are a leading cause of death. Inhibition of the noncanonical IκB kinases TANK-binding kinase...
Cardiovascular diseases, especially atherosclerosis and its complications, are a leading cause of death. Inhibition of the noncanonical IκB kinases TANK-binding kinase 1 and IKKε with amlexanox restores insulin sensitivity and glucose homeostasis in diabetic mice and human patients. Here we report that amlexanox improves diet-induced hypertriglyceridemia and hypercholesterolemia in Western diet-fed (WD-fed) Ldlr-/- mice and protects against atherogenesis. Amlexanox ameliorated dyslipidemia, inflammation, and vascular dysfunction through synergistic actions that involve upregulation of bile acid synthesis to increase cholesterol excretion. Transcriptomic profiling demonstrated an elevated expression of key bile acid synthesis genes. Furthermore, we found that amlexanox attenuated monocytosis, eosinophilia, and vascular dysfunction during WD-induced atherosclerosis. These findings demonstrate the potential of amlexanox as a therapy for hypercholesterolemia and atherosclerosis.
Topics: Aminopyridines; Animals; Atherosclerosis; Bile Acids and Salts; Diabetes Mellitus, Experimental; Humans; Hypercholesterolemia; I-kappa B Kinase; Mice; Protein Serine-Threonine Kinases
PubMed: 35917178
DOI: 10.1172/jci.insight.155552 -
Antioxidants & Redox Signaling Jan 2021Atherosclerotic cardiovascular diseases (ACVDs) continue to be a primary cause of mortality worldwide in adults aged 35-70 years, occurring more often in countries with... (Review)
Review
Atherosclerotic cardiovascular diseases (ACVDs) continue to be a primary cause of mortality worldwide in adults aged 35-70 years, occurring more often in countries with lower economic development, and they constitute an ever-growing global burden that has a considerable socioeconomic impact on society. The ACVDs encompass diverse pathologies such as coronary artery disease and heart failure (HF), among others. It is known that oxidative stress plays a relevant role in ACVDs and some of its effects are mediated by lipid oxidation. In particular, lipid peroxidation (LPO) is a process under which oxidants such as reactive oxygen species attack unsaturated lipids, generating a wide array of oxidation products. These molecules can interact with circulating lipoproteins, to diffuse inside the cell and even to cross biological membranes, modifying target nucleophilic sites within biomolecules such as DNA, lipids, and proteins, and resulting in a plethora of biological effects. This review summarizes the evidence of the effect of LPO in the development and progression of atherosclerosis-based diseases, HF, and other cardiovascular diseases, highlighting the role of protein adduct formation. Moreover, potential therapeutic strategies targeted at lipoxidation in ACVDs are also discussed. The identification of valid biomarkers for the detection of lipoxidation products and adducts may provide insights into the improvement of the cardiovascular risk stratification of patients and the development of therapeutic strategies against the oxidative effects that can then be applied within a clinical setting.
Topics: Animals; Atherosclerosis; Disease Susceptibility; Humans; Lipid Metabolism; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 32640910
DOI: 10.1089/ars.2019.7955 -
Journal of Drugs in Dermatology : JDD Aug 2023Guénin S, Kazemi A, Cline A, et al. Rethinking the inflammatory balance in psoriasis and atherosclerosis. J Drugs Dermatol. 2023;22(8):832-833....
Guénin S, Kazemi A, Cline A, et al. Rethinking the inflammatory balance in psoriasis and atherosclerosis. J Drugs Dermatol. 2023;22(8):832-833. doi:10.36849/JDD.7082.
Topics: Humans; Psoriasis; Atherosclerosis; Treatment Outcome
PubMed: 37556517
DOI: 10.36849/jdd.7082 -
Reviews in Cardiovascular Medicine Sep 2021As a potential causative factor in various cardiovascular diseases, the gut microbe-generated metabolite trimethylamine N-oxide (TMAO) has courted considerable research... (Review)
Review
As a potential causative factor in various cardiovascular diseases, the gut microbe-generated metabolite trimethylamine N-oxide (TMAO) has courted considerable research interest as a potential biomarker. TMAO is a small molecule considered to be beneficial for the health of deep-water animals due to its ability to protect proteins against hydrostatic pressure stress. However, it may cause deleterious effects in humans as mounting evidence suggests that TMAO may enhance atherosclerosis, independent of traditional risk factors. This may be mediated by its capacity to enhance inflammation, platelet activation and thrombosis, and inhibit reverse cholesterol transport. In humans, circulating levels of TMAO have been found to be associated with increased risk of developing atherosclerotic diseases such as carotid atherosclerosis, coronary atherosclerotic heart disease, stroke, and peripheral arteriosclerosis. This review aims to discuss the current role of TMAO in the atherosclerosis process, using animal models and clinical studies, with special attention to determining whether TMAO could be used as a marker for monitoring severity and prognosis in atherosclerosis and to evaluate evidence for its role as a mediator in the pathogenesis of atherosclerotic vascular disease.
Topics: Animals; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Humans; Methylamines
PubMed: 34565077
DOI: 10.31083/j.rcm2203085 -
Current Opinion in Pharmacology Oct 2022Atherosclerosis is a lipid-driven disease of the artery characterized by chronic non-resolving inflammation. Despite availability of excellent lipid-lowering therapies,... (Review)
Review
Atherosclerosis is a lipid-driven disease of the artery characterized by chronic non-resolving inflammation. Despite availability of excellent lipid-lowering therapies, atherosclerosis remains the leading cause of disability and death globally. The demonstration that suppressing inflammation prevents the adverse clinical manifestations of atherosclerosis in recent clinical trials has led to heightened interest in anti-inflammatory therapies. In this review, we briefly highlight some key anti-inflammatory and pro-resolution pathways, which could be targeted to modulate pathogenesis and stall atherosclerosis progression. We also highlight key challenges that must be overcome to turn the concept of inflammation targeting therapies into clinical reality for atherosclerotic heart disease.
Topics: Anti-Inflammatory Agents; Atherosclerosis; Coronary Artery Disease; Humans; Inflammation; Lipids
PubMed: 36037627
DOI: 10.1016/j.coph.2022.102283 -
Current Opinion in Lipidology Aug 2019Acute phase serum amyloid A (SAA) is persistently elevated in chronic inflammatory conditions, and elevated levels predict cardiovascular risk in humans. More recently,... (Review)
Review
PURPOSE OF REVIEW
Acute phase serum amyloid A (SAA) is persistently elevated in chronic inflammatory conditions, and elevated levels predict cardiovascular risk in humans. More recently, murine studies have demonstrated that over-expression of SAA increases and deficiency/suppression of SAA attenuates atherosclerosis. Thus, beyond being a biomarker, SAA appears to play a causal role in atherogenesis. The purpose of this review is to summarize the data supporting SAA as a key player in atherosclerosis development.
RECENT FINDINGS
A number of pro-inflammatory and pro-atherogenic activities have been ascribed to SAA. However, the literature is conflicted, as recombinant SAA, and/or lipid-free SAA, used in many of the earlier studies, do not reflect the activity of native human or murine SAA, which exists largely lipid-associated. Recent literatures demonstrate that SAA activates the NLRP3 inflammasome, alters vascular function, affects HDL function, and increases thrombosis. Importantly, SAA activity appears to be regulated by its lipid association, and HDL may serve to sequester and limit SAA activity.
SUMMARY
SAA has many pro-inflammatory and pro-atherogenic activities, is clearly demonstrated to affect atherosclerosis development, and may be a candidate target for clinical trials in cardiovascular diseases.
Topics: Animals; Atherosclerosis; Blood Vessels; Humans; Lipoproteins; Serum Amyloid A Protein; Thrombosis
PubMed: 31135596
DOI: 10.1097/MOL.0000000000000616 -
Current Problems in Cardiology Dec 2023Even though diagnosis and management pathways have been substantially improved over the last years, autoimmune rheumatic diseases (AIRDs) such as rheumatoid arthritis,... (Review)
Review
Even though diagnosis and management pathways have been substantially improved over the last years, autoimmune rheumatic diseases (AIRDs) such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren's syndrome, and systemic vasculitides have been linked to elevated rates of cardiovascular morbidity and mortality, primarily secondary to accelerated atherosclerosis. This phenomenon can be partially attributed to the presence of established cardiovascular risk factors but may also be a result of other inflammatory and autoimmune mechanisms that are enhanced in AIRDs. According to the current guidelines, the recommendations regarding cardiovascular disease prevention in patients with AIRDs are not significantly different from those applied to the general population. Herein, we present a review of the current literature on the risk of accelerated atherosclerosis in AIRDs and provide a summary of available recommendations for the management of cardiovascular risk in rheumatic diseases.
Topics: Humans; Cardiovascular Diseases; Risk Factors; Autoimmune Diseases; Rheumatic Diseases; Heart Disease Risk Factors; Atherosclerosis
PubMed: 37506959
DOI: 10.1016/j.cpcardiol.2023.101999