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Circulation Research Oct 2018
Review
Topics: Animals; Atherosclerosis; Autoimmunity; CD4-Positive T-Lymphocytes; Humans; Vaccination
PubMed: 30359201
DOI: 10.1161/CIRCRESAHA.118.313816 -
Arteriosclerosis, Thrombosis, and... May 2012Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune... (Review)
Review
Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics, and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits, and nonhuman primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. Although not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable.
Topics: Animals; Atherosclerosis; Disease Models, Animal; Hemodynamics; Immunity, Innate; Lipid Metabolism; Lipoproteins
PubMed: 22383700
DOI: 10.1161/ATVBAHA.111.237693 -
Circulation Research May 2022Endothelial-to-mesenchymal transition (EndMT) has been identified as a critical driver of vascular inflammation and atherosclerosis, and TGF-β (transforming growth...
BACKGROUND
Endothelial-to-mesenchymal transition (EndMT) has been identified as a critical driver of vascular inflammation and atherosclerosis, and TGF-β (transforming growth factor β) is a key mediator of EndMT. Both EndMT and atherosclerosis are promoted by disturbed flow, whereas unidirectional laminar flow limits EndMT and is atheroprotective. How EndMT and endothelial TGF-β signaling are regulated by different flow patterns is, however, still poorly understood.
METHODS
Flow chamber experiments in vitro and endothelium-specific knockout mice were used to study the role of tenascin-X in the regulation of EndMT and atherosclerosis as well as the underlying mechanisms.
RESULTS
In human endothelial cells as well as in human and mouse aortae, unidirectional laminar flow but not disturbed flow strongly increased endothelial expression of the extracellular matrix protein TN-X (tenascin-X) in a KLF4 (Krüppel-like factor 4) dependent manner. Mice with endothelium-specific loss of TN-X (EC-Tnxb-KO) showed increased endothelial TGF-β signaling as well as increased endothelial expression of EndMT and inflammatory marker genes. When EC-Tnxb-KO mice were subjected to partial carotid artery ligation, we observed increased vascular remodeling. EC-Tnxb-KO mice crossed to low-density lipoprotein receptor-deficient mice showed advanced atherosclerotic lesions after being fed a high-fat diet. Treatment of EC-Tnxb-KO mice with an anti-TGF-beta antibody or additional endothelial loss of TGF-beta receptors 1 and 2 normalized endothelial TGF-beta signaling and prevented EndMT. In in vitro studies, we found that TN-X through its fibrinogen-like domain directly interacts with TGF-β and thereby interferes with its binding to the TGF-β receptor.
CONCLUSIONS
In summary, we show that TN-X is a central mediator of flow-induced inhibition of EndMT, endothelial inflammation and atherogenesis, which functions by binding to and by blocking the activity of TGF-β. Our data identify a novel mechanism of flow-dependent regulation of vascular TGF-β, which holds promise for generating new strategies to prevent vascular inflammation and atherosclerosis.
Topics: Animals; Atherosclerosis; Cells, Cultured; Endothelial Cells; Endothelium; Epithelial-Mesenchymal Transition; Inflammation; Mice; Signal Transduction; Tenascin; Transforming Growth Factor beta
PubMed: 35443807
DOI: 10.1161/CIRCRESAHA.121.320694 -
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 -
Trends in Endocrinology and Metabolism:... Nov 2018Atherosclerosis is a chronic inflammatory and lipid-depository disease that eventually leads to acute cardiovascular events. Emerging evidence supports that epigenetic... (Review)
Review
Atherosclerosis is a chronic inflammatory and lipid-depository disease that eventually leads to acute cardiovascular events. Emerging evidence supports that epigenetic processes such as DNA methylation, histone modification, and noncoding RNAs play an important role in plaque progression and vulnerability, highlighting the therapeutic potential of epigenetic drugs in cardiovascular therapeutics.
Topics: Atherosclerosis; DNA Methylation; Enzyme Inhibitors; Epigenesis, Genetic; Histones; Humans
PubMed: 29753613
DOI: 10.1016/j.tem.2018.04.007 -
Circulation Aug 2021Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other... (Review)
Review
Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). Despite its prevalence and clinical importance, PAD has been historically underappreciated by health care professionals and patients. This underappreciation seems multifactorial (eg, limited availability of the first-line diagnostic test, the ankle-brachial index, in clinics; incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice). In the past several years, a body of evidence has indicated that these perceptions are incorrect. Several studies have consistently demonstrated that many patients with PAD are not receiving evidence-based therapies. Thus, this scientific statement provides an update for health care professionals regarding contemporary epidemiology (eg, prevalence, temporal trends, risk factors, and complications) of PAD, the present status of diagnosis (physiological tests and imaging modalities), and the major gaps in the management of PAD (eg, medications, exercise therapy, and revascularization). The statement also lists key gaps in research, clinical practice, and implementation related to PAD. Orchestrated efforts among different parties (eg, health care providers, researchers, expert organizations, and health care organizations) will be needed to increase the awareness and understanding of PAD and improve the diagnostic approaches, management, and prognosis of PAD.
Topics: American Heart Association; Atherosclerosis; Combined Modality Therapy; Diagnostic Tests, Routine; Disease Management; Disease Susceptibility; Female; Humans; Lower Extremity; Male; Mass Screening; Peripheral Arterial Disease; Prevalence; Prognosis; Public Health Surveillance; Risk Assessment; Risk Factors; Socioeconomic Factors; Treatment Outcome; United States
PubMed: 34315230
DOI: 10.1161/CIR.0000000000001005 -
European Heart Journal Sep 2022Lipid risk factors for cardiovascular disease depend in part on lifestyle, but optimum control of lipids often demands additional measures. Low-density lipoprotein (LDL)... (Review)
Review
Lipid risk factors for cardiovascular disease depend in part on lifestyle, but optimum control of lipids often demands additional measures. Low-density lipoprotein (LDL) doubtless contributes causally to atherosclerosis. Recent human genetic findings have substantiated a number of novel targets for lipid-lowering therapy including apolipoprotein C-III, angiopoietin-like protein 3 and 4, apolipoprotein V, and ATP citrate lyase. These discoveries coupled with advances in biotechnology development afford new avenues for management of LDL and other aspects of lipid risk. Beyond LDL, new treatments targeting triglyceride-rich lipoproteins and lipoprotein(a) have become available and have entered clinical development. Biological and RNA-directed agents have joined traditional small-molecule approaches, which themselves have undergone considerable refinement. Innovative targeting strategies have increased efficacy of some of these novel interventions and markedly improved their tolerability. Gene-editing approaches have appeared on the horizon of lipid management. This article reviews this progress offering insight into novel biological and therapeutic discoveries, and places them into a practical patient care perspective.
Topics: Atherosclerosis; Cardiovascular Diseases; Dyslipidemias; Humans; Hypolipidemic Agents; Lipoprotein(a); Triglycerides
PubMed: 35051271
DOI: 10.1093/eurheartj/ehab841 -
Journal of Atherosclerosis and... 2016The carotid intima-media thickness (IMT) is a widely used surrogate marker for atherosclerosis worldwide. The carotid IMT can be simply, noninvasively, and reproducibly... (Review)
Review
The carotid intima-media thickness (IMT) is a widely used surrogate marker for atherosclerosis worldwide. The carotid IMT can be simply, noninvasively, and reproducibly measured through B-mode carotid ultrasound. The carotid IMT is also a strong predictor of future cerebral and cardiovascular events. In addition, regressions of increased carotid IMT by lipid-lowering and antihypertensive drugs have been reported. Despite the strong association between increased carotid IMT and cardiovascular disease, it remains unclear whether routine carotid IMT measurement is useful for the detection of subclinical atherosclerosis in clinical practice. Researches should consider other methodological aspects, such as the definition of carotid plaques, the choice of measurement sites on the common or internal carotid artery, and the assessment of maximum or minimum IMT. The detailed guidelines for measuring carotid IMT vary by county. Thus, the usefulness of the carotid IMT may be assessed in different countries taking racial differences into account. Other important parameters revealed by carotid ultrasound, such as artery stenosis and the characteristics and size of plaques, should also be considered. Physicians should comprehensively interpret the results of carotid ultrasonography. Therefore, carotid ultrasonography is an essential tool for assessing cardiovascular risk in clinical settings.
Topics: Atherosclerosis; Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Clinical Trials as Topic; Humans; Metabolic Diseases; Risk Factors
PubMed: 26460381
DOI: 10.5551/jat.31989 -
Frontiers in Immunology 2019Atherosclerosis is a chronic low-grade inflammatory disease that affects large and medium-sized arteries and is considered to be a major underlying cause of... (Review)
Review
Atherosclerosis is a chronic low-grade inflammatory disease that affects large and medium-sized arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). The high risk of mortality by atherosclerosis has led to the development of new strategies for disease prevention and management, including immunonutrition. Plant-based dietary patterns, functional foods, dietary supplements, and bioactive compounds such as the Mediterranean Diet, berries, polyunsaturated fatty acids, ω-3 and ω-6, vitamins E, A, C, and D, coenzyme Q10, as well as phytochemicals including isoflavones, stilbenes, and sterols have been associated with improvement in atheroma plaque at an inflammatory level. However, many of these correlations have been obtained and in experimental animals' models. On one hand, the present review focuses on the evidence obtained from epidemiological, dietary intervention and supplementation studies in humans supporting the role of immunonutrient supplementation and its effect on anti-inflammatory response in atherosclerotic disease. On the other hand, this review also analyzes the possible molecular mechanisms underlying the protective action of these supplements, which may lead a novel therapeutic approach to prevent or attenuate diet-related disease, such as atherosclerosis.
Topics: Animals; Atherosclerosis; Diet; Dietary Supplements; Disease Susceptibility; Functional Food; Humans; Immunomodulation; Nutrients
PubMed: 31068933
DOI: 10.3389/fimmu.2019.00837