Biomarkers Of Atherosclerosis Research Articles

Identification of Three Cuproptosis-specific Expressed Genes as Diagnostic Biomarkers and Therapeutic Targets for Atherosclerosis.

Atherosclerosis is a chronic, inflammatory disease characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries and is considered to be a major underlying cause of cardiovascular diseases. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical implication of cuproptosis-related genes (CRGs) in atherosclerosis remains unclear. In this study, genes collected from the GEO database intersected with CRGs were identified in atherosclerosis. GSEA, GO and KEGG pathway enrichment analyses were performed for functional annotation. Through the random forest algorithm and the construction of a protein-protein interaction (PPI) network, eight selected genes (LOXL2, SLC31A1, ATP7A, SLC31A2, COA6, UBE2D1, CP and SOD1) and a vital cuproptosis-related gene FDX1 were then further validated. Two independent datasets (GSE28829 (N = 29), GSE100927 (N = 104)) were collected to construct the signature of CRGs for validation in atherosclerosis. Consistently, the atherosclerosis plaques showed significantly higher expression of SLC31A1, SLC31A2 and lower expression of SOD1 than the normal intimae. The area under the curve (AUC) of SLC31A1, SLC31A2 and SOD1 performed well for the diagnostic validation in the two datasets. In conclusion, the cuproptosis-related gene signature could serve as a potential diagnostic biomarker for atherosclerosis and may offer novel insights into the treatment of cardiovascular diseases. Based on the hub genes, a competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA and a transcription factor regulation network were ultimately constructed to explore the possible regulatory mechanism in atherosclerosis.

Interferon regulatory factor 3 is a potential biomarker to predict the process of atherosclerosis

Cardiovascular diseases is one of the major public health and medical concerns globally. Atherosclerosis is a condition where plaque build-up narrows the blood vessels, ultimately preventing sufficient blood flow to the heart. In current research, the role played by the human innate immune system in the development of atherosclerosis is a topic of interest. Although the specific relations require further studies, macrophages have been identified to play a key role in the progression of atherosclerosis due to their ability to mediate inflammation. Nevertheless, the mechanism that how macrophages cause inflammatory responses in atherosclerotic process and what is the risk factor that can describe the inflammation in clinic still remains unclear. This paper reviews the mechanism of macrophages to trigger inflammation and their relationships to atherosclerosis. In this study, Interferon Regulatory Factor 3 (IRF3) and its-related cytokine interleukin 1β was found to be upregulated in patients with acute coronary disease. Afterwards, the over-expressed IRF3 level and its RNA transcription was further confirmed in atherosclerotic ApoE-/-mice. Our results indicated that IRF3 was up-regulated during atherosclerotic process, which might be a potential biomarker of atherosclerosis and its-related coronary disease in clinic.

Role of serum lipoprotein(a) and its gene polymorphisms in cardiovascular burden among Indians: Coincidental association or causal relationship?

The increase in mortality rate due to coronary artery disease (CAD) is a major public concern among Indians. Smoking, obesity, type II diabetes are strong predisposing factors for CAD. However, the incidences of CAD in patients without these classical risk factors point to the need for identifying novel predictive biomarkers of CAD. The epidemiological studies conducted among European, African, Chinese populations, have demonstrated quite convincingly that Lipoprotein(a) is positively correlated with CAD. However, such studies are very few in the Indian context. It has been suggested that serum Lp(a) at levels more than 20mg/dL is independently associated with the risk of CAD among Indians, particularly in the young and immigrant population. Further, CAD subjects with comorbidities tend to have higher serum Lp(a) level compared to CAD subjects without any comorbidities. Genome wide association studies demonstrated that certain SNPs in the Lp (a) encoding gene (LPA), including rs10455872, rs3798220 and rs2266788 are more prevalent among Indians and are found to be strongly associated with CAD complications. Thus, based on the results of limited studies conducted in the Indian population so far, serum Lp(a) appears to be a strong and reliable risk factor for the development of CAD among Indians. However, the role of other factors like serum triglycerides, total cholesterol, homocysteine and CRP also need to be considered in determining CAD risk. The focus in this review is to highlight the recent studies on the role of Lp(a) in cardiovascular diseases in Indian population, particularly in the context of genetic polymorphisms.

MicroRNAs as Biomarkers for Coronary Artery Disease Related to Type 2 Diabetes Mellitus—From Pathogenesis to Potential Clinical Application

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD.

The Role of Transcription Factors in Coronary Artery Disease and Myocardial Infarction.

Coronary artery disease (CAD) and its main complication, myocardial infarction (MI), is a complex disease caused by environmental and genetic factors and their interaction. Family-based linkage analysis and genome-wide association studies have indicated many of genetic variations related to CAD and MI in recent years. Some are in the coding sequence, which mediates the coding protein, while others are in the non-coding region, which affects the expression of adjacent genes and forms differential gene expression. These variants and differential expressions will have varying degrees of impact on the development of the cardiovascular system and normal heart electrical activity function, subsequently leading to CAD and MI. Among these affected genes, some Transcription Factors (TFs), as important means of transcriptional regulation, have a key role in the pathogenesis of coronary artery disease and myocardial infarction. The GATAs binding protein 2 (GATA2) enhances monocyte adhesion and promoted vessel wall permeabilization through vascular EC adhesion molecule 1 (VCAM-1) upregulation, further revealing its atherosclerosis-promoting role. Myocyte enhancer factor 2 (MEF2) has a role in fostering many functions of the atherosclerotic endothelium and is a potential therapeutic target for atherosclerosis, thrombosis, and inflammation. Nuclear factor-kappa B (NF-κB) is an important promoter of vascular endothelial growth factor (VEGF)-driven angiogenesis, and its pathway has a key role in atherosclerosis-related complications such as angiogenesis, inflammation, apoptosis, and immune effects. Activating transcription factor 3 (ATF3) may be a novel prognostic biomarker and therapeutic target for atherosclerosis. The important role of signal transducer and activator of transcription 3 (STAT3) (especially in mitochondria) in endothelial cells (EC) dysfunction, inflammation, macrophage polarization and immunity in atherosclerosis.

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease.

Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery disease (CAD), which develops and progresses through a complex interplay between immune cells, vascular cells, and endothelial shear stresses. Early diagnosis of CAS is critical for avoiding plaque rupture and sudden death. Therefore, identifying new CAD biomarkers linked to vessel wall functions, such as RNA molecules with their distinct signature, is a promising development for these patients. With this rationale, the present study investigated the expression level of the vascular-related RNA transcripts (lncRNA ANRIL, miRNA-126-5p, CDK4, CDK6, TGF-β, E-cadherin, and TNF-α) implicated in the cellular vascular function, proliferation, and inflammatory processes. A case-control study design with a total of 180 subjects classified participants into two groups; CAD and control groups. The relative expression levels of the seven transcripts under study-selected using online bioinformatics tools and current literature-were assessed in the plasma of all study participants using RT-qPCR. Their predictive significance testing, scoring of disease prioritization, enrichment analysis, and the miRNA-mRNA regulatory network was investigated. The relative expression levels of all seven of the circulating vascular-related transcripts under study were statistically significant between CAD patients and controls. Receiver operating characteristic (ROC) analysis results indicated the statistical significance of all the transcripts under study with CDK4 showing the highest area under the curve (AUC) equivalent to 0.91, followed by E-cadherin (0.90), miRNA-126-5p (0.83), ANRIL (0.82), TNF-α (0.63), TGF-β (0.62), and CDK6 (0.59), in descending order. A strong association was detected between most of the transcripts studied in CAD patients with a significant Spearman's correlation coefficient with a two-tailed significance of p<0.001. Network analysis revealed a strong relationship between the five circulating vasculature transcripts studied and their target miRNAs and miR-126-5p, but not for ANRIL. The seven circulating vascular-related RNA transcripts under study could serve as potential CAD biomarkers, reflecting the cellular vascular function, proliferation, and inflammatory processes in CAD patients. Therefore, blood transcriptome analysis opens new frontiers for the non-invasive diagnosis of CAD.

The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study.

Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) - a biomarker of atherosclerosis - and assessments of macrovascular endothelial function in patients with SSc. This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT). Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25mm/h and C-reactive protein [CRP] > 5mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤmean (r = 0.370, p = 0.044) in individuals with early SSc. The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points • ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. •ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. •The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc.

Identification of potential M2 macrophage-associated diagnostic biomarkers in coronary artery disease.

M2 macrophages have been reported to be important in the progression of coronary artery disease (CAD). Thus, the present study aims at exploring the diagnostic value of M2 macrophage-associated genes in CAD. Transcriptome profile of CAD and control samples were downloaded from Gene Expression Omnibus database. The proportion of immune cells was analyzed using cell type identification by estimating relative subsets of RNA transcripts. Weighted Gene Co-expression Network Analysis (WGCNA) was carried out to screen the relevant module associated with M2 macrophages. Differential CAD and control samples of expressed genes (DEGs) were identified by the limma R package. Functional enrichment analysis by means of the clusterProfiler R package. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) algorithms were carried out to select signature genes. Receiver operating curves (ROC) were plotted to evaluate the diagnostic value of selected signature genes. The expressions of potential diagnostic markers were validated by RT-qPCR. The ceRNA network of diagnostic biomarkers was constructed via miRwalk and Starbase database. CMap database was used to screen candidate drugs in the treatment of CAD by targeting diagnostic biomarkers. A total of 166 M2 macrophage-associated genes were identified by WGCNA. By intersecting those genes with 879 DEGs, 53 M2 macrophage-associated DEGs were obtained in the present study. By LASSO, RF, and ROC analyses, C1orf105, CCL22, CRYGB, FRK, GAP43, REG1P, CALB1, and PTPN21 were identified as potential diagnostic biomarkers. RT-qPCR showed the consistent expression patterns of diagnostic biomarkers between GEO dataset and clinical samples. Perhexiline, alimemazine and mecamylamine were found to be potential drugs in the treatment of CAD. We identified eight M2 macrophage-associated diagnostic biomarkers and candidate drugs for the CAD treatment.

Hepatic fat as a novel marker for high-risk coronary atherosclerotic plaque features in familial hypercholesterolaemia

Background & aimsHepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography. MethodsWe conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles. ResultsOf 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09–2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18–1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm3 vs Q1: 414 mm3, p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed. ConclusionsHepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis.Clinical trial number: N/A.

Cardiovascular/Stroke Risk Stratification in Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study.

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients.

Polymorphism rs2383207 of CDKN2B-AS and Susceptibility to Atherosclerosis: A Mini Review.

We conducted this meta-analysis to estimate associations between CDKN2B antisense (CDKN2B-AS) rs2383207 polymorphism and susceptibility to atherosclerosis. A systematic literature research of Google Scholar and PubMed was performed to identify eligible studies. Overall, eight studies were included for meta-analyses. The association was assessed by statistical odds' ratio (OR) with 95% confidence interval (CI). RevMan software (Cochrane Collaboration, 5.3. Copenhagen) was used for the meta-analysis. Pooled overall analyses showed that rs2383207 polymorphism was associated with the risk of atherosclerosis in the whole population. Additional analyses by ethnicity revealed that rs2383207 polymorphism was associated with susceptibility to atherosclerosis in Asians and Caucasians. Our results suggest that rs2383207, might serve as genetic biomarkers of atherosclerosis. Further, studies will be required to confirm the observed association.

Identification of circular RNA BTBD7_hsa_circ_0000563 as a novel biomarker for coronary artery disease and the functional discovery of BTBD7_hsa_circ_0000563 based on peripheral blood mononuclear cells: a case control study

BackgroundBTBD7_hsa_circ_0000563 is a novel circRNA and contains conserved binding sites with RNA-binding proteins. However, BTBD7_hsa_circ_0000563 has not been fully studied in coronary artery disease (CAD). We aimed to clarify the diagnostic value and the possible functional role of BTBD7_hsa_circ_0000563 in CAD.MethodsA total of 276 human peripheral blood mononuclear cell (PBMC) samples were employed. The circularization of BTBD7_hsa_circ_0000563 was verified via Sanger sequencing. The expression level of BTBD7_hsa_circ_0000563 in CAD samples and control individuals was analysed via qRT–PCR. The diagnostic potential of BTBD7_hsa_circ_0000563 was evaluated using Spearman’s analysis, univariate and multivariable logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis. ChIRP-MS was performed to directly explore the proteins bound to BTBD7_hsa_circ_0000563. Bioinformatic analysis was conducted to investigate the possible functions and interactions of proteins bound to BTBD7_hsa_circ_0000563.ResultsIn the present study, BTBD7_hsa_circ_0000563 was verified as a circular RNA in the PBMCs of CAD patients. The expression level of BTBD7_hsa_circ_0000563 in the CAD group was significantly lower than that in the control group. The area under the ROC curve was 0.690. ChIRP-MS found seven proteins that were directly bound to BTBD7_hsa_circ_0000563. Bioinformatic analysis of these seven proteins showed that the mitophagy and DNA repair pathways were enriched. These proteins interacted with each other to a certain extent.ConclusionBTBD7_hsa_circ_0000563 may be a novel biomarker for the diagnosis of CAD and may influence the initiation and progression of CAD. These studies may reveal new possibilities for the diagnosis and treatment of CAD.

Extracellular Matrix Remodeling Biomarkers in Coronary Artery Disease.

Atherosclerosis and one of its most serious consequences, coronary artery disease, are important sources of morbidity and mortality globally, necessitating early detection and treatment. Considering their complex pathophysiology, including several harmful processes, a comprehensive approach to diagnosis, prognosis, and therapy is very desirable. Extracellular matrix remodeling is a major component of this dangerous cascade, including the cleavage of constituents (collagen, elastin, proteoglycans) and the propagation or exacerbation of the inflammatory response. Several extracellular matrix degradation indicators have been hypothesized to correlate with the existence, severity, and prognosis of coronary artery disease. The potency of matrix metalloproteinases, notably collagenases and gelatinases, has been the most thoroughly investigated in clinical studies. Stromelysins, matrilysins, transmembrane matrix metalloproteinases, collagen and laminin turnover indicators, as well as fibronectin, have also been studied to a lesser level. Among the most well-studied markers, MMP-1, MMP-2, MMP-8, and MMP-9 have been found increased in patients with cardiovascular risk factors such as metabolic syndrome, its components (obesity, dyslipidemia, diabetes mellitus), and smoking. Increasing concentrations are detected in acute coronary syndromes compared to stable angina pectoris and healthy control groups. It should also be stressed that those extracellular matrix biomarkers may also be detected in high concentrations in other vascular pathologies such as peripheral artery disease, carotid artery disease, aortic aneurysms, and dissections. Despite the advances gained, future research should focus on their importance and, more crucially, their added utility as biomarkers in identifying persons at risk of developing overt coronary artery disease. At the same time, determining the prognosis of coronary artery disease patients using such biomarkers may be important for their adequate care.

Lipoprotein-associated Phospholipase A2 in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in western societies. Therefore the identification of novel biomarkers to be used as diagnostic or therapeutic targets is of significant scientific interest. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is one such protein shown to be involved in endothelial dysfunction, vascular inflammation and atherogenesis. Several epidemiological studies have associated high Lp-PLA2 activity with an increased risk for CAD even when other CAD risk factors or inflammation markers were included in the multivariate analysis. These findings were strengthened by the results of relevant meta-analyses. However, randomized trials failed to establish Lp-PLA2 as a therapeutic target. Specifically, pharmaceutical inhibition of Lp-PLA2 when compared to the placebo failed to demonstrate a significant association with improved prognosis of patients with stable CAD or after an acute coronary syndrome (ACS). This review focuses on the available data that have investigated the potential role of Lp- PLA2 as a biomarker for CAD.

Atherosclerosis biomarkers and resting heart rate: Active players or simple bystanders?

Atherosclerosis biomarkers and resting heart rate: Active players or simple bystanders?

Resting heart rate is associated with novel plasma atherosclerosis biomarkers.

Resting heart rate (RHR) is a strong predictor of adverse cardiovascular outcomes. Both soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor for advanced glycation end products (sRAGE) are novel plasma biomarkers for atherosclerosis. In this study, we examined the potential associations between RHR and plasma sLRP1 and sRAGE levels and whether any associations might be modified by apolipoprotein E (APOE) ε4 carrier status. This cross-sectional study included 941 apparently healthy adults aged 40 years or older. Plasma sLRP1 and sRAGE levels were measured by a commercial enzyme-linked immunosorbent assay. APOE gene polymorphisms were analyzed by a polymerase chain reaction and Sanger sequencing. RHR was a significant determinant of log-transformed sLRP1 (β = 0.004; 95% confidence interval [CI], 0.002-0.007; P = 0.001) and log-transformed sRAGE (β = 0.005; 95% CI, 0.002-0.007; P <0.001) independently of age, sex, body mass index, blood pressure, blood glucose, blood lipids, lifestyle, and medical history. Additionally, APOE ε4 carrier status was inversely associated with log-transformed plasma sLRP1 level (β = -0.072; 95% CI, -0.130 to -0.015; P = 0.01) and did not modify the relationship between RHR and plasma sLRP1 level. An elevated RHR was associated with increased sLRP1 and sRAGE values, which was not modified by APOE genotype. The underlying mechanism of this effect may be relevant to the progression of atherosclerosis.

The Relationship of Carotid Intima-Media Thickness with Cell Adhesion Molecules and Pentraxin-3 in Patients with Psoriatic Arthritis

Abstract Aim Cardiovascular morbidity is increased in patients with psoriatic arthritis (PsA) compared to the general population. Several recent studies have indicated that pentraxin 3 (PTX-3) and cell adhesion molecules (CAMs) might be independent biomarkers of subclinical atherosclerosis. In this study, we aimed to determine the relationship of CAMs and PTX-3 with carotid intima media thickness (CIMT) in patients with PsA and to compare CIMT and serum levels of these biomarkers in patients with healthy controls (HCs). Method PsA patients fulfilling the CASPAR (Classification criteria for Psoriatic Arthritis) criteria without traditional cardiovascular (CV) comorbidity and HCs without autoimmune and/or CV disease were included in this cross-sectional study. Carotid artery Doppler ultrasound examinations were conducted by a single radiologist blinded to the participants’ clinical characteristics. Serum vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PTX-3 concentrations were analized. Results 43 PsA patients (27 females, mean age 42.49±11.70 years, and a mean disease duration of 9.37±7.96 years) and 37 HCs (28 females, mean age 42.16±11.38 years) were included. In regression analyses, age and PTX-3 were found to be the best predictors of CIMT in patients with PsA. CIMT was significantly higher in PsA patients compared with HCs (0.63±0.18 vs. 0.49±0.10 mm, p&lt;0.01). In te PsA group, serum levels of PTX-3, ICAM-1, and VCAM-1 were also significantly higher than HCs. CIMT correlated positively with age, disease duration, PTX-3, ICAM-1, and VCAM-1 (p&lt;0.05). Conclusion In our study, age and serum level of PTX-3 were found to be the predictors of CIMT in patients with PsA without CV comorbidity. This outcome highlights the importance of monitoring CIMT and serum level of PTX-3 as CV risk factors in PsA patients.

Changes to Urinary Proteome in High-Fat-Diet ApoE-/- Mice.

Cardiovascular disease is currently the leading cause of death worldwide. Atherosclerosis is an important pathological basis of cardiovascular disease, and its early diagnosis is of great significance. Urine bears no need nor mechanism to be stable, so it accumulates many small changes and is therefore a good source of biomarkers in the early stages of disease. In this study, ApoE-/- mice were fed a high-fat diet for 5 months. Urine samples from the experimental group and control group (C57BL/6 mice fed a normal diet) were collected at seven time points. Proteomic analysis was used for comparison within the experimental group and for comparison between the experimental group and the control group. The results of the comparison within the experimental group showed a significant difference in the urinary proteome before and after a one-week high-fat diet, and several of the differential proteins have been reported to be associated with atherosclerosis and/or as biomarker candidates. The results of the comparison between the experimental group and the control group indicated that the biological processes enriched by the GO analysis of the differential proteins correspond to the progression of atherosclerosis. The differences in chemical modifications of urinary proteins have also been reported to be associated with the disease. This study demonstrates that urinary proteomics has the potential to sensitively monitor changes in the body and provides the possibility of identifying early biomarkers of atherosclerosis.

Integrated Assessment of Macrophage Lipids Homeostasis Omics Data: Identification of Potential Genes and Pathways in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid-rich plaques within the arterial wall. Increasing evidences have shown that cellular senescence may contribute to the progression of atherosclerosis, but the mechanism remains unclear. Hence, the present study aimed to identify potential therapeutic biomarkers for atherosclerosis by analyzing the gene expression profiles of macrophages incubated with total lipoproteins. The microarray dataset no. GSE84791 obtained from Gene Expression Omnibus (GEO) database was used for this study. In the comparison of two groups: (i) THP-1 macrophage models incubated with non-LPL hydrolysed products and (ii) LPL hydrolysed products, a total of 283 differentially expressed genes (DEGs) were identified. The Gene Ontology (GO) analysis indicated that the upregulated DEGs gene set were mainly enriched in cellular response to inflammation, stress, substance uptake and intracellular transport. Besides, upregulated DEGs were significantly enriched in PPAR signalling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Notably, GO analysis revealed that the downregulated DEGs were mainly enriched in cellular proliferation, while the KEGG analysis showed that the gene set was significantly enriched in cell cycle process. The top 10 hub genes including KIF2C, NCAPG, BUB1, TOP2A, CENPF, TTK, CCNA2, PLK4, CDC6, and KIF11, was identified from the Protein-Protein Interaction (PPI) network, which constructed using STRING and further analysed using the Network Analyzer, MCODE and cytoHubba. The present study indicated that the downregulation of these genes which involved in the process of cell cycle may have an implication on atherosclerosis development.

HPA-3 and C807T polymorphisms are associated with laboratory biomarkers of coronary artery disease in Brazilian women

Reports describe the association between platelet activation, adhesion, and aggregation, as well as polymorphisms in genes encoding platelet membrane glycoproteins with a predisposition to coronary artery disease (CAD). This study investigates associations between HPA-1, -3 and C807T polymorphisms and CAD. A cross-sectional study involving 114 women who underwent coronary angiography was performed. The CAD+ group consisted of 63 women while the CAD- group of 51 women. Hematological and biochemical parameters were evaluated by electronic methods. Polymorphisms were investigated by PCR-RFLP and PCR-SSP and participants answered an epidemiological questionnaire and provided anthropometric data. Blood pressure was also measured. Statistical analyses were performed using EpiInfo v. 7.0 software. Results showed that age, diabetes mellitus, hypertension, and hyperlipidemia were associated with CAD. In addition, CAD+ women showed elevated glucose, TG, and VLDL-c levels and reduced HDL-c levels. No significant difference was observed between the allelic and genotypic distributions of the polymorphisms HPA-1, -3, and C807T in CAD+ and CAD- groups. However, CAD+ women carriers of the variant 3b allele had elevated TG and sP-selectin levels while the carriers of the variant 807T allele had reduced CT and LDL-c levels. Hence, our data suggest that the polymorphism HPA-3 increases, indirectly, the risk of CAD development and occurrence while polymorphism C807T reduces this effec.