Process Of Atherosclerosis Research Articles

Meet the First Authors.

Meet the First Authors.

Surgical Implications in the Pathology of Diabetes Mellitus – Review of the Literature

Diabetes mellitus brings together several syndromes, all burdened by a high complexity and with the potential to generate vital impairment. The large number of complications result from the association of high blood glucose level with vascular damage, neuropathy, poor healing and overall increased atherosclerosis process. The clinical manifestation of these complications involves a wide range of manifestations from simple lesions to complexpathology, many of them requiring surgical treatment. Surgical implications of diabetes mellitus include diabetic foot syndrome, soft tissue infections, renal impairment and abdominal pathology.

New Bisabolane-Type Sesquiterpenoids from Curcuma longa and Their Anti-Atherosclerotic Activity.

To explore the sesquiterpenoids in Curcuma longa L. and their activity related to anti-atherosclerosis. The chemical compounds of the rhizomes of C. longa were separated and purified by multiple chromatography techniques. Their structures were established by a variety of spectroscopic experiments. The absolute configurations were determined by comparing experimental and calculated NMR chemical shifts and electronic circular dichroism (ECD) spectra. Their anti-inflammatory effects and inhibitory activity against macrophage-derived foam cell formation were evaluated by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (ox-LDL)-injured RAW264.7 macrophages, respectively. This study resulted in the isolation of 10 bisabolane-type sesquiterpenoids (1-10) from C. longa, including two pairs of new epimers (curbisabolanones A-D, 1-4). Compound 4 significantly inhibited LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) production in RAW264.7 cells. Furthermore, compound 4 showed inhibitory activity against macrophage-derived foam cell formation, which was represented by markedly reducing ox-LDL-induced intracellular lipid accumulation as well as total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) contents in RAW264.7 cells. These findings suggest that bisabolane-type sesquiterpenoids, one of the main types of components in C. longa, have the potential to alleviate the atherosclerosis process by preventing inflammation and inhibiting macrophage foaming.

Hyperlipidemia and Cardiovascular Risk in Children and Adolescents

Atherosclerotic cardiovascular disease (ASCVD) represents the major cause of morbidity and mortality worldwide. The onset of the atherosclerosis process occurs during childhood and adolescence, subsequently leading to the onset of cardiovascular disease as young adults. Several cardiovascular risk factors can be identified in children and adolescents; however, hyperlipidemia, in conjunction with the global obesity epidemic, has emerged as the most prevalent, playing a key role in the development of ASCVD. Therefore, screening for hyperlipidemia is strongly recommended to detect high-risk children presenting with these disorders, as these patients deserve more intensive investigation and intervention. Treatment should be initiated as early as possible in order to reduce the risk of future ASCVD. In this review, we will discuss lipid metabolism and hyperlipidemia, focusing on correlations with cardiovascular risk and screening and therapeutic management to reduce or almost completely avoid the development of ASCVD.

Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review.

Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers.

Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.

Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear. Gene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe-/- mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque. We have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe-/- mice. These results point toward a promising treatment to combat atherosclerosis.

Association between cannabis use and ten-year estimated atherosclerotic cardiovascular disease risk in a middle-aged population survey

BackgroundThe association between cardiovascular (CV) risk and cannabis use remains inconsistent. The purpose of this study was to examine sex stratified associations of the different lifetime aspects of cannabis use and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk levels among the general UK Biobank population. MethodsAmong 104,092 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low, and never users. Associations between cannabis use and ASCVD risk were estimated using multiple regressions. ResultsMales presented a higher estimated 10-year ASCVD risk compared to females (7.96% vs. 2.24%, p < 0.001) and a higher proportion of heavy lifetime cannabis users (4.00% vs 2.01%, p < 0.001). In all covariate adjusted models, lifetime heavy cannabis use was associated with an increase in estimated 10-year ASCVD risk in both males and females, but with a higher effect among males (in males, B = 0.51 (0.34; 068), in females, B = 0.14 (0.05; 0.23)). When considering high estimated 10-year ASCVD risk (superior to 7.5%), similar results were observed, in males, OR=2.14 [1.82–2.51] and in females: OR=2.07 [1.35–3.17]). The current consumption of cannabis was associated with increased ASCVD risk in both males and females (p < 0.001). When considering the overall population, a significant interaction was observed between sex and cannabis use (p < 0.001). ConclusionA positive association between estimated 10-year ASCVD risk and heavy lifetime cannabis use was observed but this was higher in males. Longitudinal studies are needed in general populations to highlight the causal effects of cannabis on the atherosclerosis process.

The effect of different anti-inflammatory treatment strategies on process of atherosclerosis in ankylosing spondylitis patients

Abstract Objectives Our aim in this study was to examine the effects of different anti-inflammatory treatment strategies on the process of atherosclerosis, which is an important cause of mortality in ankylosing spondylitis (AS) patients, by examining the possible effect of treatments on inflammation, lipid profile and oxidative stress parameters in patients with AS. Methods In this study, 32 healthy volunteers served as the control group in addition to a total of 76 AS patients who were divided into two groups according to whether they were receiving anti-TNF medications or not. We assessed the levels of inflammation, oxidative stress, lipid profile parameters, and oxidized low-density lipoprotein (oxLDL). The atherogenic index of plasma (AIP), non-HDL cholesterol levels, BASDAI, and BASFI scores were also calculated. Results AS patient groups and the control group had similar lipid profile parameters, thiol-disulfide homeostasis metrics, non-HDL cholesterol, oxLDL, and AIP levels (p&gt;0.05). In contrast to AS patients receiving non-anti-TNF treatment, the BASDAI and BASFI scores, ESR, and CRP levels were lower in AS patients receiving anti-TNF treatment (p&lt;0.05). In contrast to the controls, AS patients demonstrated high TOS and OSI values (p&lt;0.05). Conclusions AS patients face increased oxidative stress that does not correlate with inflammatory status and disease activation level. Anti-TNF alpha treatment may reduce some risk factors of atherosclerotic CVD in AS patients.

A free boundary mathematical model of atherosclerosis

This paper is devoted to the study of a mathematical model of atherosclerosis in one-dimensional geometry with a free boundary. The motion of the boundary is attributable to the concentration of cells in the intima and their interaction in the subendothelial space in addition to their influx through the boundary. A mathematical model that describes the main inflammatory processes in atherosclerosis is proposed, then, by considering some simplifications, a reduced model is obtained. Using a change of variables, the reduced model is converted to a fixed boundary model with space- and time-dependent coefficients and nonlinear terms. We study the existence of solution for the fixed boundary model starting with a model with linear terms then by applying the fixed point theorem. The wave solution is as well investigated along with numerical simulations. Then, we return to the reduced model, prove the existence of solution and present numerical results. Finally, we generalize the results to the complete model initially proposed.

Color M-Mode Ultrasound to Assess Carotid Arteries: A Feasibility Study

Introduction: The gradual process of atherosclerosis involves both structural and functional changes that can accumulate over years and contribute to cardiovascular risk. We propose the use of color M-mode ultrasound to evaluate the distensibility of the carotid artery as a quantitative measurement of dynamic function that could evaluate age-related vascular change when considering atherosclerotic cardiovascular disease evaluation and risk. The aim of the study was to assess the feasibility of color M-mode ultrasound to evaluate age-related changes in the carotid arteries. Methods: Color M-mode ultrasound of the distal common carotid artery (CCA) with concurrent electrocardiogram tracing was performed on 62 adults (19 men and 43 women) in 3 age groups: young adult (20-44 years; n = 22), middle age (45-64 years; n = 20), and senior (≥65 years; n = 20). Color M-mode ultrasound images of the CCA were processed offline using ImageJ to quantify total, red, green, and blue (RGB) pixels in systole and diastole. The CCA distensibility was calculated by using the following equation: distensibility coefficient (DC) = (systolic − diastolic diameter)/(diastolic diameter × pulse pressure). The difference in ultrasound parameters among the 3 age groups was analyzed by one-way analysis of variance (ANOVA). Intraobserver and interobserver reliability of offline imaging processing was tested using intraclass correlation coefficient (ICC). Results: We observed a significant difference in CCA distensibility among the 3 age groups ( P &lt; .05). The interobserver reproducibility and intraobserver repeatability in performing offline image processing were excellent (ICC &gt;0.85). Conclusion: These findings suggest that color M-mode ultrasound is feasible in evaluating changes in CCA distensibility and systolic pixel values representing CCA blood flow significantly decreased in seniors.

Neutrophil Extracellular Traps and NLRP3 Inflammasome: A Disturbing Duo in Atherosclerosis, Inflammation and Atherothrombosis.

Atherosclerosis is the formation of plaque within arteries due to overt assemblage of fats, cholesterol and fibrous material causing a blockage of the free flow of blood leading to ischemia. It is harshly impinging on health statistics worldwide because of being principal cause of high morbidity and mortality for several diseases including rheumatological, heart and brain disorders. Atherosclerosis is perpetuated by pro-inflammatory and exacerbated by pro-coagulatory mediators. Besides several other pathways, the formation of neutrophil extracellular traps (NETs) and the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contribute significantly to the initiation and propagation of atherosclerotic plaque for its worst outcomes. The present review highlights the contribution of these two disturbing processes in atherosclerosis, inflammation and atherothrombosis in their individual as well as collaborative manner.

Evaluation of pericoronary adipose tissue attenuation on CT.

Pericoronary adipose tissue (PCAT) is the fat deposit surrounding coronary arteries. Although PCAT is part of the larger epicardial adipose tissue (EAT) depot, it has different pathophysiological features and roles in the atherosclerosis process. While EAT evaluation has been studied for years, PCAT evaluation is a relatively new concept. PCAT, especially the mean attenuation derived from CT images may be used to evaluate the inflammatory status of coronary arteries non-invasively. The most commonly used measure, PCATMA, is the mean attenuation of adipose tissue of 3 mm thickness around the proximal right coronary artery with a length of 40 mm. PCATMA can be analyzed on a per-lesion, per-vessel or per-patient basis. Apart from PCATMA, other measures for PCAT have been studied, such as thickness, and volume. Studies have shown associations between PCATMA and anatomical and functional severity of coronary artery disease. PCATMA is associated with plaque components and high-risk plaque features, and can discriminate patients with flow obstructing stenosis and myocardial infarction. Whether PCATMA has value on an individual patient basis remains to be determined. Furthermore, CT imaging settings, such as kV levels and clinical factors such as age and sex affect PCATMA measurements, which complicate implementation in clinical practice. For PCATMA to be widely implemented, a standardized methodology is needed. This review gives an overview of reported PCAT methodologies used in current literature and the potential use cases in clinical practice.

CircRNA-miRNA-mRNA network targets ubiquitin-mediated proteolysis pathway in coronary artery disease

The convoluted crosstalk of non-coding RNA (ncRNA) and mRNA results in the regulation of pathogenic processes in coronary artery disease (CAD). We utilized an in silico approach to assess circular RNA (circRNA), microRNA (miRNA), and mRNA, as potential biomarkers for CAD. CircRNA pertaining to CAD, atherosclerosis, and myocardial infarction were extracted from two databases namely Circad and circR2Disease. miRNA target sites & RNA-binding protein interactions were predicted using the circRNAinteractome database. miRNA gene targets were predicted using TargetScan, DIANA, and miRDIP. Gene enrichment analysis revealed that circRNA-miRNA distinctively targets ubiquitin-mediated proteolysis pathways (p = 0.02). Dysregulated ubiquitin pathway is known to play a role in atherosclerotic plaque progression and instability.

Acute Myocardiac Infarctions and Type 2 Diabetes Mellitus (T2DM) : a Literature Review

Diabetes mellitus (DM) is known to be a metabolic disorder happened to be chronic and identified with persistent hyperglycemia. It might be due to insulin secretion, insulin resistance or both disorders. Coronary artery disease is known to be the top killer in the world. According to WHO, as much as 17.5 million people died of cardiovascular disease. Diabetes mellitus and its correlation with coronary artery disease have been acknowledge since ages ago and known to be separate entities. As one of the risk factors, the hyperglycemia caused by DM might affect patients by enhancing the process of early atherosclerosis that attach the vital organs. This study aims to review past literature and studies regarding type 2 diabetes mellitus and acute myocardial infarctionDiabetes mellitus (DM) is known to be a metabolic disorder happened to be chronic and identified with persistent hyperglycemia. It might be due to insulin secretion, insulin resistance or both disorders. Coronary artery disease is known to be the top killer in the world. According to WHO, as much as 17.5 million people died of cardiovascular disease. Diabetes mellitus and its correlation with coronary artery disease have been acknowledge since ages ago and known to be separate entities. As one of the risk factors, the hyperglycemia caused by DM might affect patients by enhancing the process of early atherosclerosis that attach the vital organs. This study aims to review past literature and studies regarding type 2 diabetes mellitus and acute myocardial infarction

MALAT1 affects atherosclerosis by regulating endothelial cell’s microautophagy

Autophagy of vessels endothelial cells is the critical pathological process in atherosclerosis (AS). Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a kind of long non-coding RNA (lncRNA) that regulates the autophagy of vessels endothelial cells, including microautophagy. However, the relationship between AS and MALAT1 is not completely understood, and microautophagy has been ignored. In this study, I designed the experiments to research the impact of MALAT1 in endothelial cells, which could regulate the progression of AS. In the present study, I design to establish the AS model mice with low MALAT1 level. The expression level of MALAT1 needs to be detected to verify the mouse model. Then, the intensity of microautophagy of endothelial cells of mouse model and normal mouse are detected by RT-qPCR, immunofluorescence assay, and observation directly with electron microscope. The atherosclerosis progression and plaque stability are detected by comparing the rations of macrophage/vascular smooth muscle cell and collagen/lipid. This paper only provides theoretical experiment design and possible results about how MALAT1 affects AS by regulating microautophagy of vascular endothelial cells (VECs) which needs additional research in the pathology of atherosclerosis. This paper provided the possibility that MALTA1 regulates the microautophagy in VECs and MALTA1 may be the target to cure AS.

Effect of Mitochondrial Dysfunction on Coronary Artery Disease - Part 2

Organelles whose functions change as a result of molecular processes are involved in the pathogenesis of atherosclerosis, which is the main cause of coronary artery disease, in addition to molecular processes. Recently, the role of mitochondria in the pathogenesis of coronary artery disease has attracted the attention of researchers. Mitochondria is a cell organelle with its own genome that plays a regulatory role in aerobic respiration, energy production, and cell metabolism. The number of mitochondria in cells changes dynamically, and there are di���erent numbers of mitochondria in every tissue and every cell, depending on their function and energy needs. Oxidative stress causes mitochondrial dysfunction by leading to alterations in the mitochondrial genome and mitochondrial biogenesis. The dysfunctional mitochondria population in the cardiovascular system is closely related to the coronary artery disease process and cell death mechanisms. It is thought that the altered mitochondria (dys)function accompanying the molecular changes in the atherosclerosis process will be among the new therapeutic targets of coronary artery disease in the near future.

TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis.

Fibrosis is the abnormal accumulation of extracellular matrix proteins such as collagen and fibronectin. Aging, injury, infections, and inflammation can cause different types of tissue fibrosis. Numerous clinical investigations have shown a correlation between the degree of liver and pulmonary fibrosis in patients and telomere length and mitochondrial DNA content, both of which are signs of aging. Aging involves the gradual loss of tissue function over time, which results in the loss of homeostasis and, ultimately, an organism's fitness. A major feature of aging is the accumulation of senescent cells. Senescent cells abnormally and continuously accumulate in the late stages of life, contributing to age-related fibrosis and tissue deterioration, among other aging characteristics. Furthermore, aging generates chronic inflammation, which results in fibrosis and decreases organ function. This finding suggests that fibrosis and aging are closely related. The transforming growth factor-beta (TGF-β) superfamily plays a crucial role in the physiological and pathological processes of aging, immune regulation, atherosclerosis, and tissue fibrosis. In this review, the functions of TGF-β in normal organs, aging, and fibrotic tissues is discussed: TGF-β signalling is altered with age and is an indicator of pathology associated with tissue fibrosis. In addition, this review discusses the potential targeting of noncoding.

Značaj prevencije hiperhomocisteinemije kao faktora rizika za kardiovaskularne bolesti

Introduction. Homocysteine is an amino acid that is formed in the metabolism of methionine as the quantitatively most important metabolite. Its chemical structure has been known for 90 years and its biological roles are still being investigated. Under normal conditions, homocysteine is present in plasma at the concentration of 5 - 9 mmol/l. When the cell capacity for homocysteine is reached, it is transported to the extracellular space, until the intracellular level is normalized. If the cell is unable to reach the required levels of homocysteine, it accumulates in the blood and hyperhomocysteinemia occurs. Discussion. It has been determined that many factors, such as congenital enzyme deficiency, age, sex, inadequate diet (vitamin B complex deficiency) increase the level of homocysteine in the blood. Impaired kidney function, diabetes, hyperthyroidism, as well as many medications, can have an effect on homecysteinemia. Increased concentration of homocysteine in the blood accelerates the process of atherosclerosis by several different mechanisms and represents an independent risk factor for the occurrence of cardiovascular diseases and adverse cerebral events. The prevalence of hyperhomocysteinemia is estimated at 5% in the general population and 13 - 47% among patients with symptomatic atherosclerotic vascular disease. Conclusion. For these reasons, the level of homocysteine in the blood should be monitored and corrective measures should be implemented, which include sufficient intake of folic acid, vitamins B12 and B6, in doses that depend on fasting homocysteine levels and after the methionine load test.

Disruption of COMMD1 accelerates diabetic atherosclerosis by promoting glycolysis.

Diabetes will lead to serious complications, of which atherosclerosis is the most dangerous. This study aimed to explore the mechanisms of diabetic atherosclerosis. ApoE-/- mice were fed with an high-fat diet diet and injected with streptozotocin to establish an in vivo diabetic atherosclerotic model. RAW 264.7 cells were treated with oxidized low-density lipoprotein particles (ox-LDL) and high glucose to produce an in vitro diabetic atherosclerotic model. In this study, we showed that diabetes promoted the progression of atherosclerosis in ApoE-/- mice and that high glucose potentiates macrophage proinflammatory activation and foam cell formation. Mechanistically, Copper metabolism MURR1 domain-containing 1(COMMD1) deficiency increased proinflammatory activation and foam cell formation, characterized by increased glycolysis, and then accelerated the process of atherosclerosis. Furthermore, 2-Deoxy-D-glucose (2-DG) reversed this effect. Taken together, we provided evidence that the lack of COMMD1 accelerates diabetic atherosclerosis via mediating the metabolic reprogramming of macrophages. Our study provides evidence of a protective role for COMMD1 and establishes COMMD1 as a potential therapeutic strategy in patients with diabetic atherosclerosis.

Apolipoproteins as potential communicators play an essential role in the pathogenesis and treatment of early atherosclerosis.

Atherosclerosis as the leading cause of the cardiovascular disease is closely related to cholesterol deposition within subendothelial areas of the arteries. Significantly, early atherosclerosis intervention is the critical phase for its reversal. As atherosclerosis progresses, early foam cells formation may evolve into fibrous plaques and atheromatous plaque, ulteriorly rupture of atheromatous plaque increases risks of myocardial infarction and ischemic stroke, resulting in high morbidity and mortality worldwide. Notably, amphiphilic apolipoproteins (Apos) can concomitantly combine with lipids to form soluble lipoproteins that have been demonstrated to associate with atherosclerosis. Apos act as crucial communicators of lipoproteins, which not only can mediate lipids metabolism, but also can involve in pro-atherogenic and anti-atherogenic processes of atherosclerosis via affecting subendothelial retention and aggregation of low-density lipoprotein (LDL), oxidative modification of LDL, foam cells formation and reverse cholesterol transport (RCT) in macrophage cells. Correspondingly, Apos can be used as endogenous and/or exogenous targeting agents to effectively attenuate the development of atherosclerosis. The article reviews the classification, structure, and relationship between Apos and lipids, how Apos serve as communicators of lipoproteins to participate in the pathogenesis progression of early atherosclerosis, as well as how Apos as the meaningful targeting mass is used in early atherosclerosis treatment.