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Pathology International Mar 2022Atherosclerotic disease, such as myocardial infarction and stroke, is the number one killer worldwide. Atherosclerosis is considered to be caused by multiple factors,... (Review)
Review
Atherosclerotic disease, such as myocardial infarction and stroke, is the number one killer worldwide. Atherosclerosis is considered to be caused by multiple factors, including genetic and environmental factors. In humans, it takes several decades until the clinical complications develop. There are many known risk factors for atherosclerosis, including hypercholesterolemia, hypertension, diabetes and smoking, which are involved in the pathogenesis of atherosclerosis; however, it is generally believed that atherosclerosis is vascular chronic inflammation initiated by interactions of these risk factors and arterial wall cells. In the past 30 years, the molecular mechanisms underlying the pathogenesis of atherosclerosis have been investigated extensively using genetically modified animals, and lipid-reducing drugs, such as statins, have been demonstrated as the most effective for the prevention and treatment of atherosclerosis. However, despite this progress, questions regarding the pathogenesis of atherosclerosis remain and there is a need to develop new animal models and novel therapeutics to treat patients who cannot be effectively treated by statins. In this review, we will focus on two topics of atherosclerosis, "pathology" and "pathogenesis," and discuss unanswered questions.
Topics: Atherosclerosis; Humans; Risk Factors
PubMed: 35076127
DOI: 10.1111/pin.13202 -
Nature Apr 2021Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this... (Review)
Review
Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis now affects younger people, and more women and individuals from a diverse range of ethnic backgrounds, than was formerly the case. The risk factor profile has shifted as levels of low-density lipoprotein (LDL) cholesterol, blood pressure and smoking have decreased. Recent research has challenged the protective effects of high-density lipoprotein, and now focuses on triglyceride-rich lipoproteins in addition to low-density lipoprotein as causal in atherosclerosis. Non-traditional drivers of atherosclerosis-such as disturbed sleep, physical inactivity, the microbiome, air pollution and environmental stress-have also gained attention. Inflammatory pathways and leukocytes link traditional and emerging risk factors alike to the altered behaviour of arterial wall cells. Probing the pathogenesis of atherosclerosis has highlighted the role of the bone marrow: somatic mutations in stem cells can cause clonal haematopoiesis, which represents a previously unrecognized but common and potent age-related contributor to the risk of developing cardiovascular disease. Characterizations of the mechanisms that underpin thrombotic complications of atherosclerosis have evolved beyond the 'vulnerable plaque' concept. These advances in our understanding of the biology of atherosclerosis have opened avenues to therapeutic interventions that promise to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.
Topics: Animals; Atherosclerosis; Disease Susceptibility; Humans; Inflammation; Models, Biological; Plaque, Atherosclerotic; Risk Factors
PubMed: 33883728
DOI: 10.1038/s41586-021-03392-8 -
Signal Transduction and Targeted Therapy Apr 2022Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage... (Review)
Review
Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors. Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis. Several signaling pathways, that are associated with the inflammatory response, have been implicated within atherosclerosis such as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt signaling pathways, which are of importance for atherosclerosis development and regression. Targeting inflammatory pathways, especially the NLRP3 inflammasome pathway and its regulated inflammatory cytokine interleukin-1β, could represent an attractive new route for the treatment of atherosclerotic diseases. Herein, we summarize the knowledge on cellular participants and key inflammatory signaling pathways in atherosclerosis, and discuss the preclinical studies targeting these key pathways for atherosclerosis, the clinical trials that are going to target some of these processes, and the effects of quelling inflammation and atherosclerosis in the clinic.
Topics: Atherosclerosis; Genome-Wide Association Study; Humans; Inflammasomes; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction
PubMed: 35459215
DOI: 10.1038/s41392-022-00955-7 -
Nature Reviews. Disease Primers Aug 2019Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many... (Review)
Review
Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease.
Topics: Atherosclerosis; Drug Therapy; Humans; Hyperlipidemias; Mass Screening; Risk Factors
PubMed: 31420554
DOI: 10.1038/s41572-019-0106-z -
Medicina Clinica Sep 2020The recognition of atherogenesis as an active process rather than a passive cholesterol storage disease has underlined key inflammatory mechanisms. Hence, innate and... (Review)
Review
The recognition of atherogenesis as an active process rather than a passive cholesterol storage disease has underlined key inflammatory mechanisms. Hence, innate and adaptive immune responses play an important role in the onset and progression of atherosclerosis. More recently, some clinical studies were designed to address the impact of anti-inflammatory intervention strategies in reducing risk of cardiovascular disease beyond the management of classic risk factors. Therefore, we review first the pathophysiological contribution of inflammation to atherosclerosis and the effect of lipid-lowering drugs on inflammatory biomarkers. Next, we address the effect of classic anti-inflammatory drugs, pharmacological therapies targeting specific inflammatory mediators and vaccines in cardiovascular prevention.
Topics: Anti-Inflammatory Agents; Atherosclerosis; Biomarkers; Humans; Inflammation; Inflammation Mediators
PubMed: 32571617
DOI: 10.1016/j.medcli.2020.04.024 -
International Journal of Molecular... Mar 2020Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin... (Review)
Review
Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin secretion, insulin action, or both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, and carbohydrates. Atherosclerosis develops as a result of a multistep process ultimately leading to cardiovascular disease associated with high morbidity and mortality. Alteration of lipid metabolism is a risk factor and characteristic feature of atherosclerosis. Possible links between the two chronic disorders depending on altered metabolic pathways have been investigated in numerous studies. It was shown that both types of diabetes mellitus can actually induce atherosclerosis development or further accelerate its progression. Elevated glucose level, dyslipidemia, and other metabolic alterations that accompany the disease development are tightly involved in the pathogenesis of atherosclerosis at almost every step of the atherogenic process. Chronic inflammation is currently considered as one of the key factors in atherosclerosis development and is present starting from the earliest stages of the pathology initiation. It may also be regarded as one of the possible links between atherosclerosis and diabetes mellitus. However, the data available so far do not allow for developing effective anti-inflammatory therapeutic strategies that would stop atherosclerotic lesion progression or induce lesion reduction. In this review, we summarize the main aspects of diabetes mellitus that possibly affect the atherogenic process and its relationship with chronic inflammation. We also discuss the established pathophysiological features that link atherosclerosis and diabetes mellitus, such as oxidative stress, altered protein kinase signaling, and the role of certain miRNA and epigenetic modifications.
Topics: Animals; Atherosclerosis; Diabetes Mellitus; Glucose; Humans; Inflammation; Insulin Resistance; Lipids; Oxidative Stress
PubMed: 32155866
DOI: 10.3390/ijms21051835 -
European Journal of Preventive... Mar 2020Despite major efforts to reduce atherosclerotic cardiovascular disease (ASCVD) burden with conventional risk factor control, significant residual risk remains. Recent... (Review)
Review
Despite major efforts to reduce atherosclerotic cardiovascular disease (ASCVD) burden with conventional risk factor control, significant residual risk remains. Recent evidence on non-traditional determinants of cardiometabolic health has advanced our understanding of lifestyle-disease interactions. Chronic exposure to environmental stressors like poor diet quality, sedentarism, ambient air pollution and noise, sleep deprivation and psychosocial stress affect numerous traditional and non-traditional intermediary pathways related to ASCVD. These include body composition, cardiorespiratory fitness, muscle strength and functionality and the intestinal microbiome, which are increasingly recognized as major determinants of cardiovascular health. Evidence points to partially overlapping mechanisms, including effects on inflammatory and nutrient sensing pathways, endocrine signalling, autonomic function and autophagy. Of particular relevance is the potential of low-risk lifestyle factors to impact on plaque vulnerability through altered adipose tissue and skeletal muscle phenotype and secretome. Collectively, low-risk lifestyle factors cause a set of phenotypic adaptations shifting tissue cross-talk from a proinflammatory milieu conducive for high-risk atherosclerosis to an anti-atherogenic milieu. The ketone body ß-hydroxybutyrate, through inhibition of the NLRP-3 inflammasome, is likely to be an intermediary for many of these observed benefits. Adhering to low-risk lifestyle factors adds to the prognostic value of optimal risk factor management, and benefit occurs even when the impact on conventional risk markers is discouragingly minimal or not present. The aims of this review are (a) to discuss novel lifestyle risk factors and their underlying biochemical principles and (b) to provide new perspectives on potentially more feasible recommendations to improve long-term adherence to low-risk lifestyle factors.
Topics: Atherosclerosis; Healthy Lifestyle; Heart Disease Risk Factors; Humans; Life Style; Protective Factors; Risk Assessment; Risk Reduction Behavior
PubMed: 31408370
DOI: 10.1177/2047487319869400 -
Cardiovascular Research Mar 2022This review aims at summarizing updated evidence on cardiovascular disease (CVD) risk associated with consumption of specific food items to substantiate dietary... (Review)
Review
This review aims at summarizing updated evidence on cardiovascular disease (CVD) risk associated with consumption of specific food items to substantiate dietary strategies for atherosclerosis prevention. A systematic search on PubMed was performed to identify meta-analyses of cohort studies and RCTs with CVD outcomes. The evidence is highly concordant in showing that, for the healthy adult population, low consumption of salt and foods of animal origin, and increased intake of plant-based foods-whole grains, fruits, vegetables, legumes, and nuts-are linked with reduced atherosclerosis risk. The same applies for the replacement of butter and other animal/tropical fats with olive oil and other unsaturated-fat-rich oil. Although the literature reviewed overall endorses scientific society dietary recommendations, some relevant novelties emerge. With regard to meat, new evidence differentiates processed and red meat-both associated with increased CVD risk-from poultry, showing a neutral relationship with CVD for moderate intakes. Moreover, the preferential use of low-fat dairies in the healthy population is not supported by recent data, since both full-fat and low-fat dairies, in moderate amounts and in the context of a balanced diet, are not associated with increased CVD risk; furthermore, small quantities of cheese and regular yogurt consumption are even linked with a protective effect. Among other animal protein sources, moderate fish consumption is also supported by the latest evidence, although there might be sustainability concerns. New data endorse the replacement of most high glycemic index (GI) foods with both whole grain and low GI cereal foods. As for beverages, low consumption not only of alcohol, but also of coffee and tea is associated with a reduced atherosclerosis risk while soft drinks show a direct relationship with CVD risk. This review provides evidence-based support for promoting appropriate food choices for atherosclerosis prevention in the general population.
Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Diet; Fruit; Humans; Risk Factors; Vegetables
PubMed: 34229346
DOI: 10.1093/cvr/cvab173 -
International Journal of Molecular... Jul 2022The development and pathogenesis of atherosclerosis are significantly influenced by lifestyle, particularly nutrition. The modern level of science and technology... (Review)
Review
The development and pathogenesis of atherosclerosis are significantly influenced by lifestyle, particularly nutrition. The modern level of science and technology development promote personalized nutrition as an efficient preventive measure against atherosclerosis. In this survey, the factors were revealed that contribute to the formation of an individual approach to nutrition: genetic characteristics, the state of the microbiota of the gastrointestinal tract (GIT) and environmental factors (diets, bioactive components, cardioprotectors, etc.). In the course of the work, it was found that in order to analyze the predisposition to atherosclerosis associated with nutrition, genetic features affecting the metabolism of nutrients are significant. The genetic features include the presence of single nucleotide polymorphisms (SNP) of genes and epigenetic factors. The influence of telomere length on the pathogenesis of atherosclerosis and circadian rhythms was also considered. Relatively new is the study of the relationship between chrono-nutrition and the development of metabolic diseases. That is, to obtain the relationship between nutrition and atherosclerosis, a large number of genetic markers should be considered. In this relation, the question arises: "How many genetic features need to be analyzed in order to form a personalized diet for the consumer?" Basically, companies engaged in nutrigenetic research and choosing a diet for the prevention of a number of metabolic diseases use SNP analysis of genes that accounts for lipid metabolism, vitamins, the body's antioxidant defense system, taste characteristics, etc. There is no set number of genetic markers. The main diets effective against the development of atherosclerosis were considered, and the most popular were the ketogenic, Mediterranean, and DASH-diets. The advantage of these diets is the content of foods with a low amount of carbohydrates, a high amount of vegetables, fruits and berries, as well as foods rich in antioxidants. However, due to the restrictions associated with climatic, geographical, material features, these diets are not available for a number of consumers. The way out is the use of functional products, dietary supplements. In this approach, the promising biologically active substances (BAS) that exhibit anti-atherosclerotic potential are: baicalin, resveratrol, curcumin, quercetin and other plant metabolites. Among the substances, those of animal origin are popular: squalene, coenzyme Q10, omega-3. For the prevention of atherosclerosis through personalized nutrition, it is necessary to analyze the genetic characteristics (SNP) associated with the metabolism of nutrients, to assess the state of the microbiota of the GIT. Based on the data obtained and food preferences, as well as the individual capabilities of the consumer, the optimal diet can be selected. It is topical to exclude nutrients of which their excess consumption stimulates the occurrence and pathogenesis of atherosclerosis and to enrich the diet with functional foods (FF), BAS containing the necessary anti-atherosclerotic, and stimulating microbiota of the GIT nutrients. Personalized nutrition is a topical preventive measure and there are a number of problems hindering the active use of this approach among consumers. The key factors include weak evidence of the influence of a number of genetic features, the high cost of the approach, and difficulties in the interpretation of the results. Eliminating these deficiencies will contribute to the maintenance of a healthy state of the population through nutrition.
Topics: Animals; Atherosclerosis; Diet; Genetic Markers; Nutritional Status; Vegetables
PubMed: 35897799
DOI: 10.3390/ijms23158233 -
Circulation Research Jan 2022Resolution is an active and highly coordinated process that occurs in response to inflammation to limit tissue damage and promote repair. When the resolution program... (Review)
Review
Resolution is an active and highly coordinated process that occurs in response to inflammation to limit tissue damage and promote repair. When the resolution program fails, inflammation persists. It is now understood that failed resolution is a major underlying cause of many chronic inflammatory diseases. Here, we will review the major failures of resolution in atherosclerosis, including the imbalance of proinflammatory to pro-resolving mediator production, impaired clearance of dead cells, and functional changes in immune cells that favor ongoing inflammation. In addition, we will briefly discuss new concepts that are emerging as possible regulators of resolution and highlight the translational significance for the field.
Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; Humans; Inflammasomes; Signal Transduction
PubMed: 34995137
DOI: 10.1161/CIRCRESAHA.121.319822