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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 -
Journal of Atherosclerosis and... 2016Lecithin:cholesterol acyltransferase (LCAT) is the only enzyme capable of esterifying cholesterol in plasma, thus determining the maturation of high-density... (Review)
Review
Lecithin:cholesterol acyltransferase (LCAT) is the only enzyme capable of esterifying cholesterol in plasma, thus determining the maturation of high-density lipoproteins. Because it maintains an unesterified cholesterol gradient between peripheral cells and extracellular acceptors, for a long time, LCAT has been considered as a key enzyme in reverse cholesterol transport. However, despite the fact that it has been more than 50 years since the identification of LCAT, the role of this enzyme in the pathogenesis of atherosclerosis is still debated. A number of studies have been conducted in different animal models, with contradictory results. Studies in humans, in particular in the general population, in subjects at high cardiovascular risk, and in carriers of genetic LCAT deficiency in an excellent model to evaluate the correlation between the reduction of LCAT activity and atherosclerosis also gave conflicting results. This review provides a comprehensive overview of the controversial findings obtained in animals and humans, strengthening the necessity of further investigation to establish how LCAT could be regulated in a promising therapeutic strategy to reduce cardiovascular risk.
Topics: Animals; Atherosclerosis; Humans; Phosphatidylcholine-Sterol O-Acyltransferase; Risk Factors
PubMed: 26607351
DOI: 10.5551/jat.32854 -
Wiley Interdisciplinary Reviews.... Jan 2017Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts... (Review)
Review
Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts with the adhesion of inflammatory monocytes on the activated endothelial cells in response to inflammatory stimuli. These monocytes can further migrate into the intimal layer of the blood vessel where they differentiate into macrophages, which take up oxidized low-density lipoproteins and release inflammatory factors to amplify the local inflammatory response. After accumulation of cholesterol, the lipid-laden macrophages are transformed into foam cells, the hallmark of the early stage of atherosclerosis. Foam cells can die from apoptosis or necrosis, and the intracellular lipid is deposed in the artery wall forming lesions. The angiogenesis for nurturing cells is enhanced during lesion development. Proteases released from macrophages, foam cells, and other cells degrade the fibrous cap of the lesion, resulting in rupture of the lesion and subsequent thrombus formation. Thrombi can block blood circulation, which represents a major cause of acute heart events and stroke. There are generally no symptoms in the early stages of atherosclerosis. Current detection techniques cannot easily, safely, and effectively detect the lesions in the early stages, nor can they characterize the lesion features such as the vulnerability. While the available therapeutic modalities cannot target specific molecules, cells, and processes in the lesions, nanoparticles appear to have a promising potential in improving atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells, endothelial cells, angiogenesis, proteolysis, apoptosis, and thrombosis. Indeed, many nanoparticles have been developed in improving blood lipid profile and decreasing inflammatory response for enhancing therapeutic efficacy of drugs and decreasing their side effects. WIREs Nanomed Nanobiotechnol 2017, 9:e1412. doi: 10.1002/wnan.1412 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Atherosclerosis; Disease Models, Animal; Endothelial Cells; Humans; Mice; Monocytes; Nanoparticles; Rats; Theranostic Nanomedicine
PubMed: 27241794
DOI: 10.1002/wnan.1412 -
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 Lipidology Aug 2018We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease... (Review)
Review
PURPOSE OF REVIEW
We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature.
RECENT FINDINGS
We focus on original research in humans or in human tissues. Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, including carotid-intima media thickness, vascular reactivity and calcification in people with Type 1 (T1D) and Type 2 (T2D) diabetes as well as nondiabetic dysglycaemia. In addition, observational studies have provided novel insights into the mechanisms of metformin's effects on carotid plaque, monocytes/macrophages, vascular smooth muscle and endothelial cells, including via 5'-adenosine monophosphate-activated protein kinase (AMPK) activation.
SUMMARY
Recent trials based on surrogate outcome measures have provided further data suggesting protective effects of metformin against vascular disease in youth and adults with Type 1 diabetes, as well as in adults with prediabetes and Type 2 diabetes. In parallel, human tissue and cell studies have provided new insights into pleiotropic effects of metformin and suggest novel drug targets. As metformin is an inexpensive agent with an established safety profile, larger scale clinical trials based on hard clinical outcomes [cardiovascular disease (CVD) events] are now indicated.
Topics: Atherosclerosis; Blood Vessels; Humans; Lipid Metabolism; Metformin
PubMed: 29878903
DOI: 10.1097/MOL.0000000000000532 -
Vascular Pharmacology Mar 2019Cardiovascular disease (CVD), the leading cause of death and morbidity in the Western world, begins with lipid accumulation in the arterial wall, which is the initial... (Review)
Review
Cardiovascular disease (CVD), the leading cause of death and morbidity in the Western world, begins with lipid accumulation in the arterial wall, which is the initial step in atherogenesis. Alterations in lipid metabolism result in increased risk of cardiometabolic disorders, and treatment of lipid disorders remains the most common strategy aimed at reducing the incidence of CVD. Work done over the past decade has identified numerous classes of non-coding RNA molecules including microRNAs (miRNAs) and long-non-coding RNAs (lncRNAs) as critical regulators of gene expression involved in lipid metabolism and CVD, mostly acting at post-transcriptional level. A number of miRNAs, including miR-33, miR-122 and miR-148a, have been demonstrated to play important role in controlling the risk of CVD through regulation of cholesterol homeostasis and lipoprotein metabolism. lncRNAs are recently emerging as important regulators of lipid and lipoprotein metabolism. However, much additional work will be required to fully understand the impact of lncRNAs on CVD and lipid metabolism, due to the high abundance of lncRNAs and the poor-genetic conservation between species. This article reviews the role of miRNAs and lncRNAs in lipid and lipoprotein metabolism and their potential implications for the treatment of CVD.
Topics: Animals; Arteries; Atherosclerosis; Gene Expression Regulation; Humans; Lipid Metabolism; Plaque, Atherosclerotic; RNA, Untranslated; Signal Transduction
PubMed: 29929012
DOI: 10.1016/j.vph.2018.06.011 -
Current Atherosclerosis Reports May 2016Historically, the relationship between exercise and the cardiovascular system was viewed as unidirectional, with a disease resulting in exercise limitation and hazard.... (Review)
Review
Historically, the relationship between exercise and the cardiovascular system was viewed as unidirectional, with a disease resulting in exercise limitation and hazard. This article reviews and explores the bidirectional nature, delineating the effects, generally positive, on the cardiovascular system and atherosclerosis. Exercise augments eNOS, affects redox potential, and favorably affects mediators of atherosclerosis including lipids, glucose homeostasis, and inflammation. There are direct effects on the vasculature as well as indirect benefits related to exercise-induced changes in body composition and skeletal muscle. Application of aerobic exercise to specific populations is described, with the hope that this knowledge will move the science forward and improve individual patient outcome.
Topics: Atherosclerosis; Body Composition; Cardiovascular Diseases; Cardiovascular System; Exercise; Humans; Physical Fitness
PubMed: 27005804
DOI: 10.1007/s11883-016-0580-7 -
Discovery Medicine Feb 2015Significant progress has been made in understanding in the pathogenesis of atherosclerosis. Nevertheless, atherosclerosis remains a great threat to human health... (Review)
Review
Significant progress has been made in understanding in the pathogenesis of atherosclerosis. Nevertheless, atherosclerosis remains a great threat to human health worldwide. Epigenetic mechanisms, which involve DNA methylation, histone modification, and microRNA, have significantly enhanced our understanding of the pathological process of atherosclerosis. More importantly, epigenetic processes (in contrast to genetic alterations) are reversible and thus provide a potential therapeutic target in atherosclerosis treatment. Both in vitro and in vivo studies using drugs targeting enzymes involved in epigenetic modifications have shown considerable promise in atherosclerosis treatment. This review aims to present an overview of current epigenetic mechanisms involved in the pathogenesis of atherosclerosis, and discuss points in these processes where therapeutic interventions likely bear fruition.
Topics: Atherosclerosis; Biomarkers; Epigenesis, Genetic; Humans
PubMed: 25725221
DOI: No ID Found -
Current Pediatric Reviews 2017Cardiovascular diseases are the leading cause of death worldwide. While cardiovascular disease typically does not occur until adulthood, the pathogenesis of... (Review)
Review
BACKGROUND
Cardiovascular diseases are the leading cause of death worldwide. While cardiovascular disease typically does not occur until adulthood, the pathogenesis of atherosclerotic cardiovascular disease starts in early childhood.
OBJECTIVE
The purpose of this review is to describe the evidence that the process of atherosclerosis begins in childhood, as well as identify the risk factors present in childhood that are associated with the presence of atherosclerotic cardiovascular disease in childhood as well as future cardiovascular events in adulthood.
RESULTS AND CONCLUSION
There is much accumulating evidence linking modifiable risk factors that are already present in childhood and that strongly predict future cardiovascular disease. The selective targeting of modifiable risk factors in childhood, including body mass index, holds promise in reducing the burden of adult cardiovascular disease. Future research studies should focus on elucidating the mechanisms which drive the pathogenesis of atherosclerosis in childhood and young adulthood, as well as identifying which interventions are most effective at limiting the progression of atherosclerosis and thus reducing future cardiovascular disease.
Topics: Adolescent; Adult; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Child; Humans; Risk Factors
PubMed: 29345597
DOI: 10.2174/1573396314666180117092010 -
Biochimica Et Biophysica Acta.... May 2018Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all... (Review)
Review
Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all global deaths. Current treatments for CVD, such as optimized statin therapy, are associated with considerable residual risk and several side effects in some patients. The outcome of research on the identification of alternative pharmaceutical agents for the treatment of CVD has been relatively disappointing with many promising leads failing at the clinical level. Nutraceuticals, products from food sources with health benefits beyond their nutritional value, represent promising agents in the prevention of CVD or as an add-on therapy with current treatments. This review will highlight the potential of several nutraceuticals, including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti-CVD therapies based on clinical and pre-clinical mechanism-based studies.
Topics: Animals; Atherosclerosis; Dietary Supplements; Fatty Acids, Unsaturated; Flavonoids; Humans; Polyphenols
PubMed: 29454074
DOI: 10.1016/j.bbadis.2018.02.006