Development Of Atherosclerosis Research Articles

Association of subclinical carotid artery atherosclerosis assessed by carotid ultrasound with nonalcoholic fatty liver disease fibrosis score in young and middle-aged men.

Non-alcoholic Fatty Liver Disease (NAFLD) is a widespread liver disorder caused by excess fat accumulation in the liver with no significant alcohol consumption. This condition has been linked to the development of cardiovascular diseases (CVD) and atherosclerosis. Carotid intima-media thickness (CIMT) and carotid plaques, which are established markers of subclinical atherosclerosis, were used to assess CVD risk. However, few studies have explored the correlation between NAFLD and subclinical atherosclerosis, especially in young and middle-aged men. A study on 200 male patients aged 18-55 years aimed to investigate the association between NAFLD fibrosis score (NFS) and CIMT, as well as carotid plaque presence. The study, conducted between July 2023 and January 2024, included CIMT measurements and plaque assessments performed using B-mode ultrasound. Participants were divided into two groups based on CIMT values and plaque presence, and NFS was analyzed for its association with CIMT and plaque. Participants with higher CIMT values had a significantly higher NFS (-2.9 ± 1.13 vs. -1.9 ± 1.4, P < 0.001) than those with lower CIMT values. Similarly, participants with carotid plaque also exhibited a higher NFS (-2.5 ± 1.3 vs. -1.7 ± 1.4, P = 0.002). Multivariate logistic regression analysis showed that NFS was a strong predictor of both increased CIMT (odds ratio [OR]: 1.564%95 CI 1.035-2.363; P = 0.034) and carotid plaque presence (OR: 1.605%95 CI 1.118-2.290; P = 0.010). These results emphasize the potential role of NFS as a marker of subclinical atherosclerosis in young and middle-aged men.

Anthocyanins as natural bioactives with anti-hypertensive and atherosclerotic potential: Health benefits and recent advances

BackgroundHypertension is a highly prevalent chronic metabolic illness affecting individuals of all age groups. Furthermore, it is a significant risk factor for the development of atherosclerosis (AS), as a correlation between hypertension and AS has been observed. However, the effective treatments for either of these disorders appear to be uncommon. MethodsA systematic search of articles published in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar databases over the last decade was performed using the following keywords: hypertension, AS, anthocyanins, antioxidants, gut microbes, health benefits, and bioactivity. ResultsThe available research indicates that anthocyanin consumption can achieve antioxidant effects by inducing the activation of intracellular nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, previous reports showed that anthocyanins can enhance the human body's ability to fight against inflammation and cancer through the inhibition of inflammatory factors and the regulation of related signaling pathways. They can also protect the blood vessels and nervous system by regulating the production and function of endothelial nitric oxide synthase (eNOS). Gut microorganisms play an important role in various chronic diseases. Our research has also investigated the role of anthocyanins in the metabolism of the gut microbiota, leading to significant breakthroughs. This study not only presents a unique strategy for reducing the risk of cardiovascular diseases (CVDs) without the need for medicine but also provides insights into the development and utilization of intestinal probiotic dietary supplements. ConclusionIn this review, different in vitro and in vivo studies have shown that anthocyanins slow down the onset and progression of hypertension and AS through different mechanisms. In addition, gut microbial metabolites also play a crucial role in diseases through the gut-liver axis.

Metabolomics and network pharmacology exploration of the effects of bile acids on carotid atherosclerosis and potential underlying mechanisms.

Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks. In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology. (1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets. This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

Assessment of the Concentrations of Selected Aminothiols in Patients after COVID-19.

Background: Data show that due to endothelial damage and thrombogenic effects, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may accelerate the development of atherosclerosis and increase the risk of cardiovascular diseases (CVDs). The impaired metabolism of aminothiols increases oxidative stress, as these molecules are involved in antioxidant defense as well as in thiol redox control. In this study, total levels of selected aminothiols (i.e., cysteine (Cys), homocysteine (HCy), and glutathione) in convalescents after coronavirus disease of 2019 (COVID-19) were evaluated. The analyses were made according to the sex of the patients, time from COVID-19 onset, and COVID-19 severity. Methods: The study group consisted of 212 patients after COVID-19. Levels of total aminothiols were assessed in the blood plasma using high-performance liquid chromatography (HPLC). Results: The mean Cys concentrations were higher in men than in women (229.92 µmol/L ± 51.54 vs. 210.35 µmol/L ± 41.90, respectively; p = 0.003). Differences in Cys levels were also noticed in the total study group between patients distinguished due to time from disease onset (226.82 µmol/L ± 40.57 in <12 weeks, 232.23 µmol/L ± 47.99 in patients 12-24 weeks, and 208.08 µmol/L ± 48.43 in patients >24 weeks; p = 0.005). In addition, over 11% of total patients 12-24 weeks from disease onset had Cys levels above 300 µmol/L compared to almost 4% of patients <12 weeks and 2% of patients >24 weeks (p = 0.046). In sex-adjusted subgroups, significant differences due to time from COVID-19 were found in Cys levels in women (p = 0.004) and in glutathione levels in men (p = 0.024). None of the aminothiol levels differed between the subgroups based on the severity of COVID-19. Conclusions: Men had overall higher Cys levels than women. Cys levels were lower >24 weeks after COVID-19 onset than in the earlier period after disease onset. A partial elevation in Cys levels 12-24 weeks after the disease onset may contribute to the increase in CVD risk in the post-COVID-19 period.

The impact of lipoprotein(a) level on cardiac pathologies in diabetes: a cardiac CT study.

We aimed to explore the imaging profile of coronary atherosclerosis, perivascular inflammation, myocardial perfusion, and interstitial fibrosis in diabetes stratified by lipoprotein(a) [Lp(a)] levels. In this prospective study, we enrolled diabetic patients who had undergone computed tomography (CT) angiography, stress CT-myocardial perfusion imaging, and late iodine enhancement in 20 months. Then, we categorized them into elevated and normal groups based on an Lp(a) cutoff level of 30 mg/dL. All imaging data, including coronary atherosclerosis parameters, pericoronary adipose tissue (PCAT) density, stress myocardial blood flow (MBF), and extracellular volume (ECV), were collected for further analysis. In total, 207 participants (mean age: 59.1 ± 12.0 years, 111 males) were included in this study. Patients with elevated Lp(a) level had more pronounced percent atheroma volume (2.55% (1.01-9.01%) versus 1.30% (0-4.95%), p = 0.010), and demonstrated a higher incidence of positive remodeling, spotty calcification, and high-risk plaque (HRP) than those with normal Lp(a) levels (75.6% versus 54.8%, p = 0.015; 26.8% versus 9.6%, p = 0.003; 51.2% versus 30.1%, p = 0.011, respectively). Results of the multivariate analysis revealed that after adjusting for all clinical characteristics, elevated Lp(a) levels were an independent parameter associated with HRP (odds ratio = 2.608; 95% confidence interval: 1.254-5.423, p = 0.010). However, no significant difference was found between the two groups in terms of PCAT density, stress MBF, and ECV. Elevated Lp(a) levels are associated with extensive coronary atherosclerosis and HRP development. However, they are not related to perivascular inflammation, decreased myocardial perfusion, and interstitial fibrosis in diabetes. Elevated lipoprotein(a) levels are associated with extensive coronary atherosclerosis and a high incidence of HRPs. However, they are not related to perivascular inflammation, decreased myocardial perfusion, and interstitial fibrosis in diabetes. Diabetes is a known risk factor that accelerates cardiovascular disease progression. Diabetics with elevated lipoprotein(a) (Lp(a)) levels had a higher percent atheroma volume and positive remodeling, spotty calcification, and HRPs. Patients with diabetes should be screened for elevated Lp(a) using CCTA for comprehensive evaluation of atherosclerotic characteristics.

Features of Coronary Atherosclerosis in Patients with Coronary Artery Disease Residing in the Far North

Aim: To evaluate the features of coronary artery disease (CAD) in patients in the Far North and determination of the potential impact of extreme climatic factors on the development of coronary atherosclerosis. Material and Methods. Using the “Register of performed coronary angiography operations”, 5,679 patients with coronary artery disease were selected, who underwent coronary angiography at the Tyumen Cardiology Research Center. The main study group consisted of 2,590 patients permanently residing in the YamaloNenets Autonomous Okrug and 3,089 patients residing in the South of the Tyumen Region. Results. Patients with permanent residence in the Yamalo-Nenets Autonomous Okrug were on average younger (53.20 ± 7.49 versus 56.79 ± 8.34 years, p &lt; 0.001), men were more common among them. In the extreme North there were more smokers (40.7 vs. 32.0%, p &lt; 0.001) and alcohol users (19.7 vs.15.0%, p &lt; 0.001), and more frequent myocardial infarction in anamnesis (57.1 vs. 48.2%, p &lt; 0.001). At the same time, in patients permanently residing in the South of the Tyumen Region, a burdened hereditary history of CAD was more often determined, and the frequency of arterial hypertension and dyslipidemia was higher. In groups balanced by baseline clinical and demographic characteristics, including CAD risk factors, patients from the Yamal-Nenets Autonomous Okrug had more frequent lesions of the three main coronary arteries: anterior descending artery (42 vs. 35%, p &lt; 0.001), circumflex artery (25 vs. 23%, p = 0.038) and right coronary artery (42 vs. 38%, p = 0.007). It should be noted that in balanced groups in patients permanently residing in the Far North, occlusive lesions of the coronary arteries were statistically significantly more likely to be determined (54 vs. 47%, p &lt; 0.001). Also, between the compared groups, statistically significant differences were found in the type of left ventricle (LV) myocardial remodeling, but these differences were not determined in the balanced groups. Also, in the group of patients permanently residing in the Far North, there was a trend towards a decrease in the LV ejection fraction (53.6 ± 8.6% vs. 54.2 ± 8.7, p = 0.074).Conclusion. In patients with verified coronary artery disease living in the Far North, a more frequent and pronounced atherosclerotic lesion of the coronary bed is determined. These pathological changes are probably due to the complex impact of unfavorable natural and climatic environmental factors.

Dissecting the role of cannabinoids in vascular health and disease.

Cannabis, often recognized as the most widely used illegal psychoactive substance globally, has seen a shift in its legal status in several countries and regions for both recreational and medicinal uses. This change has brought to light new evidence linking cannabis consumption to various vascular conditions. Specifically, there is an association between cannabis use and atherosclerosis, along with conditions such as arteritis, reversible vasospasm, and incidents of aortic aneurysm or dissection. Recent research has started to reveal the mechanisms connecting cannabinoid compounds to atherosclerosis development. It is well known that the primary biological roles of cannabinoids operate through the activation of cannabinoid receptor types 1 and 2. Manipulation of the endocannabinoid system, either genetically or pharmacologically, is emerging as a promising approach to address metabolic dysfunctions related to obesity. Additionally, numerous studies have demonstrated the vasorelaxant properties and potential atheroprotective benefits of cannabinoids. In preclinical trials, cannabidiol is being explored as a treatment option for monocrotaline-induced pulmonary arterial hypertension. Although existing literature suggests a direct role of cannabinoids in the pathogenesis of atherosclerosis, the correlation between cannabinoids and other vascular diseases was only reported in some case series or observational studies, and its role and precise mechanisms remain unclear. Therefore, it is necessary to summarize and update previously published studies. This review article aims to summarize the latest clinical and experimental research findings on the relationship between cannabis use and vascular diseases. It also seeks to shed light on the potential mechanisms underlying these associations, offering a comprehensive view of current knowledge in this evolving field of study.

Development and disease-specific regulation of RNA splicing in cardiovascular system.

Alternative splicing is a complex gene regulatory process that distinguishes itself from canonical splicing by rearranging the introns and exons of an immature pre-mRNA transcript. This process plays a vital role in enhancing transcriptomic and proteomic diversity from the genome. Alternative splicing has emerged as a pivotal mechanism governing complex biological processes during both heart development and the development of cardiovascular diseases. Multiple alternative splicing factors are involved in a synergistic or antagonistic manner in the regulation of important genes in relevant physiological processes. Notably, circular RNAs have only recently garnered attention for their tissue-specific expression patterns and regulatory functions. This resurgence of interest has prompted a reevaluation of the topic. Here, we provide an overview of our current understanding of alternative splicing mechanisms and the regulatory roles of alternative splicing factors in cardiovascular development and pathological process of different cardiovascular diseases, including cardiomyopathy, myocardial infarction, heart failure and atherosclerosis.

Early growth response factor 3 may regulate coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression

AimThe present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1β, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. MethodsWe recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1β and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. ResultsThe levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1β in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r = 0.55, p < 0.001), IL-1β levels (r = 0.21, p = 0.004) and the Gensini score (r = 0.20, p = 0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. ConclusionsIn the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.

Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment.

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B 6 and vitamin B 12 folic acid (vitamin B 9 ). Causes of HHcy include deficiency of vitamins B 6 , B 9 , and B 12 , genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B 6 , and vitamin B 12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B 6 , vitamin B 12 , omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.

Monocyte Subsets in Cardiovascular Disease: A Biomarker Perspective.

Endothelial dysfunctions together with a dysregulated immune response and lipid accumulation are important confounding factors in the onset and chronic development of atherosclerosis. Recently, a large body of data has emerged on the sequential involvement of different immune cell types, including monocytes, in the pathology of this disease. In this condensed review, we aim to highlight some of the recent basic research and clinical findings on monocyte subsets published since our joint European Society of Cardiology consensus document, and re-evaluate their potential relevance as surrogate biomarkers in coronary artery disease.

Reparative effects after low-dose radiation exposure: Inhibition of atherosclerosis by reducing NETs release

ObjectiveThe cardiovascular system effects of environmental low-dose radiation exposure on radiation practitioners remain uncertain and require further investigation. The aim of this study was to initially investigate and explore the mechanisms by which low-dose radiation may contribute to atherosclerosis through a multi-omics joint comprehensive basic experiment. MethodsWe used WGCNA and differential analyses to identify shared genes and potential pathways between radiation injury and atherosclerosis sequencing datasets, as well as tissue transcriptome immune infiltration level extrapolation and single-cell transcriptome data correction using the CIBERSORT deconvolution algorithm. Animal models were constructed by combining a high-fat diet with 5 Gy γ-ray whole-body low-dose ionizing radiation. The detection of NETs release was validated by enzyme-linked immunosorbent assay. ResultsAnalysis reveals shared genes in both datasets of post-irradiation and atherosclerosis, suggesting that immune system neutrophils may be a key node connecting radiation to atherosclerosis. NETs released by neutrophil death can influence the development of atherosclerosis. Animal experiments showed that the number of neutrophils decreased (P < 0.05) and the concentration of NETs reduced after low-dose radiation compared with the control group, and the concentration of NETs significantly increased (P < 0.05) in the HF group. Endothelial plaques were significantly increased in the high-fat feed group and significantly decreased in the low-dose radiation group compared with the control group. ConclusionsLong-term low-dose ionizing radiation exposure stimulates neutrophils and inhibits their production of NETs, resulting in inhibition of atherosclerosis.

Atherosclerosis associated with Chlamydia pneumoniae: Dissecting the etiology

Chlamydia pneumoniae related infections and atherosclerosis are both common entities. Today, the literature presents an enormous amount of data regarding the role of C. pneumoniae in the development and sustainment of atherosclerosis and allowing us to comprehend the molecular mechanisms behind better. The implications of C. pneumoniae in atherogenesis include altered platelet function, hypercoagulability, macrophage dysfunction, vascular smooth muscle proliferation, and increased neutrophilic migration. Therefore, it would not be wrong to implicate that, C. pneumoniae plays important roles in almost every stage of atherogenesis. Furthermore, various serological markers suggestive of active or past C. pneumoniae infection are known to be associated with multiple clinical presentations, such as abdominal aortic aneurysms, subclinical atherosclerosis in the young individuals, aggravated atherosclerosis in heterozygous familial hypercholesterolemia. This review, as a result, aims to provide detailed insights into the pathophysiological mechanisms of atherogenesis associated with C. pneumoniae and its clinical implications.

Targeting Ferroptosis: A Novel Strategy for the Treatment of Atherosclerosis.

Since ferroptosis was reported in 2012, its application prospects in various diseases have been widely considered, initially as a treatment direction for tumors. Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis. The primary mechanism is to affect the occurrence and development of atherosclerosis through intracellular iron homeostasis, ROS and lipid peroxide production and metabolism, and a variety of intracellular signaling pathways. Inhibition of ferroptosis is effective in inhibiting the development of atherosclerosis, and it can bring a new direction for treating atherosclerosis. In this review, we discuss the mechanism of ferroptosis and focus on the relationship between ferroptosis and atherosclerosis, summarize the different types of ferroptosis inhibitors that have been widely studied, and discuss some issues worthy of attention in the treatment of atherosclerosis by targeting ferroptosis.

Effect of Diets with the Addition of Edible Insects on the Development of Atherosclerotic Lesions in ApoE/LDLR-/- Mice.

Foods enriched with insects can potentially prevent several health disorders, including cardiovascular diseases, by reducing inflammation and improving antioxidant status. In this study, Tenebrio molitor and Gryllus assimilis were selected to determine the effect on the development of atherosclerosis in ApoE/LDLR-/- mice. Animals were fed AIN-93G-based diets (control) with 10% Tenebrio molitor (TM) and 10% Gryllus assimilis (GA) for 8 weeks. The nutritional value as well as antioxidant activity of selected insects were determined. The lipid profile, liver enzyme activity, and the fatty acid composition of liver and adipose tissue of model mice were evaluated. Quantitative analysis of atherosclerotic lesions in the entire aorta was performed using the en face method, and for aortic roots, the cross-section method was used. The antioxidant status of the GA cricket was significantly higher compared to the TM larvae. The results showed that the area of atherosclerosis (en face method) was not significantly different between groups. Dietary GA reduced plaque formation in the aortic root; additionally, significant differences were observed in sections at 200 and 300 µm compared to other groups. Furthermore, liver enzyme ALT activity was lower in insect-fed groups compared to the control group. The finding suggests that a diet containing edible insect GA potentially prevents atherosclerotic plaque development in the aortic root, due to its high antioxidant activity.

The Strength in Breakdown: Understanding Mitophagy and Its Implications in Cardiovascular Diseases

Mitophagy, the selective autophagy of mitochondria, plays a crucial role in maintaining cellular homeostasis by ensuring the quality and quantity of functional mitochondria. This process is essential for cellular health, as dysfunctional mitochondria can lead to severe pathological conditions, including cardiovascular disorders, cancer, and neurodegenerative diseases. Impaired mitophagy may result in abnormal mitochondrial morphology and DNA mutations, contributing to the progression of these ailments. Therefore, understanding the mechanisms regulating mitophagy and its implications in pathological contexts is of great importance. This review paper provides an in-depth exploration of the mechanisms of mitophagy and its role in maintaining mitochondrial quality. It summarizes the most recent findings in the field, particularly focusing on the implications of defective mitophagy in cardiovascular disorders. The study delves into the connections between impaired mitophagy and the development of atherosclerosis, ischemic heart disease, cardiomyopathies, hypertension, and peripheral vascular disease. Moreover, it discusses the various regulatory proteins and processes involved in mitophagy, presenting a comprehensive overview of the intricate network governing this crucial cellular process. By shedding light on the intricate mechanisms involved in mitophagy and its role in addressing cardiovascular disorders, this review paper paves the way for potential therapeutic targets aimed at mitigating mitochondrial dysfunction-related ailments. The identification of pathways and proteins associated with mitophagy provides valuable insights into potential interventions that could prevent or effectively treat these disorders. However, it also highlights the existing uncertainties and the need for further in-depth exploration to fully comprehend the complexity of mitophagy regulation and its broader implications in cellular health.

Aqueous PM2.5 promotes lipid accumulation, classical macrophage polarisation and heat shock response

Fine particulate matter (PM2.5) is an air pollutant that enhances susceptibility to cardiovascular diseases. Macrophages are the first immune cells to encounter the inhaled particles and orchestrate an inflammatory response. Given their role in atherosclerosis development, we investigated whether aqueous PM2.5 could elicit atherogenic effects by polarising macrophages to a pro-oxidative and pro-inflammatory phenotype and enhancing foam cell formation. The RAW264.7 macrophage cell line was exposed to PM2.5 for 48 h, with PBS as the control. Aqueous PM2.5 induced apoptosis and reduced cell proliferation. In surviving cells, we observed morphological, phagocytic, oxidative, and inflammatory features (i.e. enhanced iNOS, Integrin-1β, IL-6 expression), indicative of classical macrophage activation. We also detected an increase in total and surface HSP70 levels, suggesting macrophage activation. Further, exposure of high-cholesterol diet-fed mice to PM2.5 resulted in aortic wall enlargement, indicating vascular lesions. Macrophages exposed to PM2.5 and non-modified low-density lipoprotein (LDL) showed exacerbated lipid accumulation. Given the non-oxidised LDL used and the evidence linking inflammation to disrupted cholesterol negative feedback, we hypothesise that PM2.5-induced inflammation in macrophages enhances their susceptibility to transforming into foam cells. Finally, our results indicate that exposure to aqueous PM2.5 promotes classical macrophage activation, marked by increased HSP70 expression and that it potentially contributes to atherosclerosis.

ABCA1 deficiency causes tissue-specific dysregulation of the SREBP2 pathway in mice

ABCA1 plays an essential role in the formation of high-density lipoprotein (HDL), and its mutations cause Tangier disease (TD), a familial HDL deficiency. In addition to the disappearance of HDL, TD patients exhibit cholesterol deposition in peripheral tissues through a mechanism poorly understood, which may contribute to the development of premature atherosclerosis. We and others previously showed that ABCA1 deficiency causes hyperactivation of the SREBP2 pathway in vitro. Here, we show using Abca1 knockout mice that ABCA1 deficiency leads to tissue-specific dysregulation of SREBP2 activity in a nutritional status-dependent manner, which may underlie the pathophysiology of TD.

Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population

BackgroundAtherosclerosis is an inflammatory disease. Interleukin 18 (IL-18) is an inflammatory molecule that has been linked to the development of atherosclerosis and cardiovascular disease. ObjectiveTo evaluate the possible relationship between plasma levels of IL-18 and the presence of atherosclerosis evaluated at the carotid level, as well as to analyze the possible modulation by different polymorphisms in a Mediterranean population. Material and methods746 individuals from the metropolitan area of ​​Valencia were included, recruited over a period of 2 years. Hydrocarbon and lipid metabolism parameters were determined using standard methodology and IL-18 using ELISA. In addition, carotid ultrasound was performed and the genotype of 4 SNPs related to the IL-18 signaling pathway was analyzed. ResultsPatients with higher plasma levels of IL-18 had other associated cardiovascular risk factors. Elevated IL-18 levels were significantly associated with higher carotid IMT and the presence of atheromatous plaques. The genotype with the A allele of the SNP rs2287037 was associated with a higher prevalence of carotid atheromatous plaque. On the contrary, the genotype with the C allele of the SNP rs2293224 was associated with a lower prevalence of atheromatous plaque. ConclusionsHigh levels of IL-18 were significantly associated with a higher carotid IMT and the presence of atheromatous plaques, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the IL-18 receptor gene and the presence of atheroma plaque.

Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1−/−Ldlr−/− mice

Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na+ taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon-like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models. In humans, a genetic loss-of-function variant of NTCP has been associated with reduced plasma cholesterol levels. Here, we aimed to assess if Bulevirtide treatment attenuates atherosclerosis development by treating female Ldlr−/− mice with Bulevirtide or vehicle for 11 weeks. Since this did not result in the expected increase in plasma bile salt levels, we generated Oatp1a1−/−Ldlr−/− mice, an atherosclerosis-prone model with human-like hepatic bile salt uptake characteristics. These mice showed delayed plasma clearance of bile salts and elevated bile salt levels upon Bulevirtide treatment. At the study endpoint, Bulevirtide-treated female Oatp1a1−/−Ldlr−/− mice had reduced atherosclerotic lesion area in the aortic root that coincided with lowered plasma LDL-c levels, independent of intestinal cholesterol absorption. In conclusion, Bulevirtide, which is considered safe and is EMA-approved for the treatment of Hepatitis D, reduces atherosclerotic lesion area by reducing plasma LDL-c levels. We anticipate that its application may extend to atherosclerotic cardiovascular diseases, which warrants clinical trials.