Cause Of Atherosclerosis Research Articles

A Study to Assess the Effectiveness of Video Assisted Teaching Programme on Knowledge Regarding Prevention of Coronary Artery Disease among Students In A Selected Arts College of Durg, Chhattisgarh (State)

Coronary artery disease is an obstructed blood flow through the coronary arteries to the heart muscles. The primary cause of coronary artery disease is atherosclerosis. The term acute coronary syndrome is used to encompass the continuum of coronary artery disease. Coronary artery disease is most prevalent type of cardiovascular disease in adults, more death occurs in middle aged adults. In India, even younger age group are prone to get heart disease due to their health damaging life style. This study was conducted to assess the effectiveness of video assisted teaching programme on knowledge regarding prevention of coronary artery disease among students in a selected arts college of Durg, Chhattisgarh (State) The conceptual framework used in this study was based on J.W.Kenney’s open system model. A quantitative approach was used for the present study. Using purposive sampling technique,60 arts students were selected and video assisted teaching given after pre-test. Followed by that post test was conducted on day 7, the collected data was analyzed using descriptive and inferential statistics. The overall analysis of prevention of coronary artery disease the mean post-test knowledge score of the subjects 28.07 is higher than the mean pre-test knowledge score 18.17. Thecalculated‘t’ value 19.769nis greater than of table value (1.984) at 0.001 level of significance. This indicates that video assited teaching programme was effective in gaining knowledge regarding the prevention of coronary artery disease. The association between socio demographic variables with pre-test knowledge score significance (p<0.001) was tested. Based on the findings indicate that there is a significant difference between pre-test and post-test knowledge score on prevention of coronary artery disease in a selected arts college students at Durg.

A baculoviral gene and drug-eluting (GDES) stent to promote re-endothelialization and prevent restenosis caused by atherosclerosis

Abstract Background Coronary artery disease (CAD) is a prevalent condition affecting approximately one in every 20 individuals over the age of 20, resulting in significant health and economic burdens worldwide. Atherosclerosis, characterized by plaque buildup in the arteries, is a leading cause of CAD, involving endothelial dysfunction, inflammation, and smooth muscle cell hyperproliferation. The standard interventions for CAD, namely bare-metal stents (BMS) or drug-eluting stents (DES), often lead to complications such as blood clotting, inflammation, and arterial re-narrowing, necessitating further interventions and potentially leading to severe outcomes like heart failure, stroke, or death. Additionally, the TGFβ1 gene regulates SMC proliferation and ECM secretion, promoting endothelial cell proliferation, inhibiting smooth muscle cell hyperproliferation, reducing reactive oxygen species production. Purpose This innovative stent aims to mitigate complications associated with conventional stents by promoting endothelial health and preventing inflammation and hyperproliferation downstream. The purpose of this study is to design a new gene and drug eluting stent and evaluate their preclinical efficacy and safety in addressing some of the key limitations of currently available coronary stents. Methods The TGFβ1 expressing baculoviruses loaded PLGA nanoparticles are prepared by double emulsion solvent evaporation method. The formulated nanoparticles were characterized by their surface morphology, particle size, zeta potential, and in vitro release. Moreover, the designed nanoparticles undergo a further investigation for their therapeutic efficiency using cell lines. The GDES is synthesized by dip-coating a BMS into a solution containing Everolimus and genipin carrying baculoviruses expressing TGFβ1 in nanoparticles. The stent elutes the gene and drug over specific durations pertaining to a sustained release profile. The study assesses the functionality and safety of the GDES through in vitro and in vivo experiments, including cell culture studies and animal models. Results The PLGA nanoparticles at 115.3±1.4 nm with a polydipersity (pdi) index of 0.152 have a sustained release profile for the TGFβ1 expressing baculovirus. The findings demonstrate that the GDES effectively promotes endothelial health and prevents inflammation and hyperproliferation downstream. The expression of TGFβ1 facilitates the formation of a fully reconstituted endothelial lining, reducing the risk of complications. Additionally, the prolonged release of Everolimus prevents inflammation and the progression of neointimal hyperplasia. The stent coating and system exhibit non-cytotoxicity and hemocompatibility, ensuring safety during expansion and degradation over time. Overall, the combined action of gene and drug elution in the GDES shows promising results in addressing current complications associated with cardiovascular stents.

Unraveling the proteomic signatures of coronary artery disease and hypercholesterolemia.

Atherosclerosis, a leading cause of coronary artery disease (CAD), is heavily influenced by hypercholesterolemia (HC). Proteomics research has shown promise in identifying biological markers for CAD diagnosis and prognosis. This cross-sectional study aimed to identify novel biomarkers for detecting HC and CAD. Through the analysis of proteome data from healthy controls (n=45) and patients diagnosed with HC (n=51) or CAD (n=32), distinct protein patterns associated with each condition were identified. Significant alterations in protein levels were identified with a false discovery rate (FDR)-corrected q-value of <0.05. Subsequent receiver operating characteristic (ROC) analysis, with an area under the curve (AUC) greater than 0.75, was conducted. CAD patients exhibited significantly increased levels of the cholesterol-metabolizing protein PCSK9 and varied levels of the angiogenesis-related protein SDF-1 compared to controls. In pairwise comparisons among the study groups, 65 proteins showed significant differential expression. Notably, 14 of these proteins had significant correlations with blood cholesterol levels. Additionally, 22 of the identified proteins were associated with CAD or HC pathways, with nine proteins being common to both conditions (Apo E, Apo E3, MMP-3, PCSK9, SDF-1, Apo B, PAFAH, HSP 60, and TAK1-TAB1). Nevertheless, this is an exploratory study, and validation studies are needed to confirm these potential protein biomarkers for CAD in the context of HC.

Mitigating Vascular Inflammation by Mimicking AIBP Mechanisms: A New Therapeutic End for Atherosclerotic Cardiovascular Disease

Atherosclerosis, characterized by the accumulation of lipoproteins and lipids within the vascular wall, underlies a heart attack, stroke, and peripheral artery disease. Endothelial inflammation is the primary component driving atherosclerosis, promoting leukocyte adhesion molecule expression (e.g., E-selectin), inducing chemokine secretion, reducing the production of nitric oxide (NO), and enhancing the thrombogenic potential. While current therapies, such as statins, colchicine, anti-IL1β, and sodium–glucose cotransporter 2 (SGLT2) inhibitors, target systemic inflammation, none of them addresses endothelial cell (EC) inflammation, a critical contributor to disease progression. Targeting endothelial inflammation is clinically significant because it can mitigate the root cause of atherosclerosis, potentially preventing disease progression, while reducing the side effects associated with broader anti-inflammatory treatments. Recent studies highlight the potential of the APOA1 binding protein (AIBP) to reduce systemic inflammation in mice. Furthermore, its mechanism of action also guides the design of a potential targeted therapy against a particular inflammatory signaling pathway. This review discusses the unique advantages of repressing vascular inflammation or enhancing vascular quiescence and the associated benefits of reducing thrombosis. This approach offers a promising avenue for more effective and targeted interventions to improve patient outcomes.

Wall Shear Stress (WSS) Analysis in Atherosclerosis in Partial Ligated Apolipoprotein E Knockout Mouse Model through Computational Fluid Dynamics (CFD).

Atherosclerosis involves an inflammatory response due to plaque formation within the arteries, which can lead to ischemic stroke and heart disease. It is one of the leading causes of death worldwide, with various contributing factors such as hyperlipidemia, hypertension, obesity, diabetes, and smoking. Wall shear stress (WSS) is also known as a contributing factor of the formation of atherosclerotic plaques. Since the causes of atherosclerosis cannot be attributed to a single factor, clearly understanding the mechanisms and causes of its occurrence is crucial for preventing the disease and developing effective treatment strategies. To better understand atherosclerosis and define the correlation between various contributing factors, computational fluid dynamics (CFD) analysis is primarily used. CFD simulates WSS, the frictional force caused by blood flow on the vessel wall with various hemodynamic changes. Using apolipoprotein E knockout (ApoE-KO) mice subjected to partial ligation and a high-fat diet at 1-week, 2-week, and 4-week intervals as an atherosclerosis model, CFD analysis was conducted along with the reconstruction of carotid artery blood flow via magnetic resonance imaging (MRI) and compared to the inflammatory factors and pathological staining. In this experiment, a comparative analysis of the effects of high WSS and low WSS was conducted by comparing the standard deviation of time-averaged wall shear stress (TAWSS) at each point within the vessel wall. As a novel approach, the standard deviation of TAWSS within the vessel was analyzed with the staining results and pathological features. Since the onset of atherosclerosis cannot be explained by a single factor, the aim was to find the correlation between the thickness of atherosclerotic plaques and inflammatory factors through standard deviation analysis. As a result, the gap between low WSS and high WSS widened as the interval between weeks in the atherosclerosis mouse model increased. This finding not only linked the occurrence of atherosclerosis to WSS differences but also provided a connection to the causes of vulnerable plaques.

Unidirectional association of clonal hematopoiesis with atherosclerosis development

Clonal hematopoiesis, a condition in which acquired somatic mutations in hematopoietic stem cells lead to the outgrowth of a mutant hematopoietic clone, is associated with a higher risk of hematological cancer and a growing list of nonhematological disorders, most notably atherosclerosis and associated cardiovascular disease. However, whether accelerated atherosclerosis is a cause or a consequence of clonal hematopoiesis remains a matter of debate. Some studies support a direct contribution of certain clonal hematopoiesis-related mutations to atherosclerosis via exacerbation of inflammatory responses, whereas others suggest that clonal hematopoiesis is a symptom rather than a cause of atherosclerosis, as atherosclerosis or related traits may accelerate the expansion of mutant hematopoietic clones. Here we combine high-sensitivity DNA sequencing in blood and noninvasive vascular imaging to investigate the interplay between clonal hematopoiesis and atherosclerosis in a longitudinal cohort of healthy middle-aged individuals. We found that the presence of a clonal hematopoiesis-related mutation confers an increased risk of developing de novo femoral atherosclerosis over a 6-year period, whereas neither the presence nor the extent of atherosclerosis affects mutant cell expansion during this timeframe. These findings indicate that clonal hematopoiesis unidirectionally promotes atherosclerosis, which should help translate the growing understanding of this condition into strategies for the prevention of atherosclerotic cardiovascular disease in individuals exhibiting clonal hematopoiesis.

Common ground on immune infiltration landscape and diagnostic biomarkers in diabetes-complicated atherosclerosis: an integrated bioinformatics analysis.

Type 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis (AS). However, definitive evidence regarding the common molecular mechanisms underlying these two diseases are lacking. This study aimed to investigate the mechanisms underlying the association between T2DM and AS. The gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein-protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor-mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed. A total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein-protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis. In this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.

Vascular endothelial cells of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage.

Atherosclerosis is essentially the leading factor behind occurrences of cardiovascular diseases (CVDs)-associated incidents, while mitochondrial dysfunction is also the main cause of atherosclerosis. The present study conducted a comparative analysis of mitochondrial function-related indicators in cholesterol-induced vascular endothelial cells (VECs) from Mongolian gerbils, Sprague-Dawley (SD) rats and humans. It reported that the inhibitory effect of cholesterol treatment on the viability of Mongolian gerbil VECs was markedly lower than the other two types of VECs at the same concentration. Following cholesterol treatment, mitochondrial DNA copy numbers, reactive oxygen species level, calcium concentration and mitochondrial membrane potential of Mongolian gerbil VECs did not change markedly. These results suggested that the function of mitochondria in the VECs of Mongolian gerbil is normal. Additionally, cholesterol treatment also did not alter the levels of superoxide dismutase, glutathione peroxidase, ATP, NADH-CoQ reductase and cytochrome c oxidase in Mongolian gerbil VECs. It was hypothesized that the VECs of Mongolian gerbils have certain resistance to oxidative damage induced by cholesterol. In brief, the present study demonstrated that VECs of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage. The aforementioned findings establish a theoretical foundation for the advancement of innovative strategies in the prevention and treatment of atherosclerosis.

The Influence of Balneotherapy Using Salty Sulfide-Hydrogen Sulfide Water on Selected Markers of the Cardiovascular System: A Prospective Study.

Background: The sulfide-hydrogen sulfide brine balneotherapy (HSBB), including a combination of dissolved hydrogen sulfide (H2S) gas, inorganic sulfur ions (S2-), and hydrosulfide ions (HS-), is one of the most important and most effective forms of spa treatment in patients with osteoarticular disorders (OADs). Some cardiovascular diseases (CVDs) are often considered to be contraindications to HSBB since the presence of thiol groups may lead to an increased quantity of reactive oxygen species (ROS), which damage the vascular endothelium, and endothelial dysfunction is considered to be the main cause of atherosclerosis. However, there are a number of literature reports suggesting this theory to be false. H2S is a member of the endogenous gaseous transmitter family and, since it is a relatively recent addition, it has the least well-known biological properties. H2S-NO interactions play an important role in oxidative stress in CVDs. The general objective of this study was to assess the cardiovascular safety of HSBB and analyze the effect of HSBB on selected cardiovascular risk markers. Methods: A total of 100 patients at the age of 76.3 (±7.5) years from the Włókniarz Sanatorium in Busko-Zdrój were initially included in the study. The following parameters were assessed: age, sex, height, body weight, body surface area (BSA), body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), heart rate, the diagnosis of OAD that was the indication for balneotherapy, creatinine (CREAT), glomerular filtration rate (GFR), lipid panel, C-reactive protein (CRP), uric acid (UA), and fibrinogen (FIBR) and cardiovascular markers: (cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP). Results: A significant decrease in DBP and a trend towards SBP reduction were observed over the course of the study. A significant decrease was observed in CRP levels decreasing from 2.7 (±3.6) mg/L to 2.06 (±1.91) mg/L, whereas FIBR rose significantly from 2.95 (±0.59) g/L to 3.23 (±1.23) g/L. LDL-C levels decreased slightly, statistically significant, from 129.36 (±40.67) mg/dL to 123.74 (±36.14) mg/dL. HSBB did not affect the levels of evaluated cardiovascular biomarkers, namely NT-proBNP (137.41 (±176.52) pg/mL vs. 142.89 (±182.82) pg/mL; p = 0.477) and cTnT (9.64 (±4.13) vs. 9.65 (±3.91) ng/L; p = 0.948). A multiple regression analysis of pre-balneotherapy and post-balneotherapy values showed cTnT levels to be independently correlated only with CREAT levels and GFR values. None of the assessed parameters independently correlated with the NT-proBNP level. Conclusions: HSBB resulted in a statistically significant improvement in a subclinical pro-inflammatory state. HSBB has a beneficial effect in modifying key cardiovascular risk factors by reducing LDL-C levels and DBP values. HSBB has a neutral effect on cardiovascular ischemia/injury. Despite slightly elevated baseline levels of the biochemical marker of HF (NT-proBNP), HSBB causes no further increase in this marker. The use of HSBB in patients with OAD has either a neutral effect or a potentially beneficial effect on the cardiovascular system, which may constitute grounds for further studies to verify the current cardiovascular contraindications for this form of therapy.

CircZNF609 sponges miR-135b to up-regulate SEMA3A expression to alleviate ox-LDL-induced atherosclerosis.

The initiation and progression of atherosclerotic plaque caused by abnormal lipid metabolism is one of the main causes of atherosclerosis (AS). Lipid droplet accumulation has become a novel research pointcut for AS treatment in recent years. In AS patients, miR-135b level was up-regulated relative to the normal cases, which showed negative correlations with the levels of Semaphorin 3A (SEMA3A) and circZNF609, separately. The U937-derived macrophages were cultured with ox-LDL to establish AS models in vitro. After that, the lipid accumulation, inflammation, mitochondrial dysfunction and cell death were evaluated by ORO, ELISA, RT-qPCR, western blot, JC-1 and FCM assaysrespectively. Transfection of the circZNF609 expressionvector notably declined lipid accumulation, attenuated inflammation, reduced mitochondrial dysfunction and inhibited cell death in ox-LDL-stimulated cells. The direct binding of miR-135b to circZNF609 in vitro was confirmed using RIP assay, and SEMA3A expression was up-regulated by circZNF609 overexpression. After manipulating the endogenous expressions of circZNF609, miR-135b and SEMA3A, the above damages in ox-LDL-stimulated cells were rescued by inhibition of miR-135b expression and overexpression of circZNF609 or SEMA3A. Besides, the AS mice model was built to demonstrate the excessive lipid accumulation, increasing inflammation and cell death in AS pathogenesis according to the results of HE staining, ELISA and IHC assays, while these damages were reversed after overexpression of circZNF609 or SEMA3A. In AS models, overexpressed circZNF609 prevents the AS progression through depleting miR-135b expression and subsequent up-regulation of SEMA3A expression to overwhelm lipid accumulation, mitochondrial dysfunction and cell death.

The Relationship between Renal Resistive Index and Complexity of Coronary Lesions in Patients with Stable Coronary Artery Diseases.

The most common cause of coronary artery diseases (CAD) is atherosclerosis. The synergy between percutaneous coronary intervention with TAXUS™ and cardiac surgery (SYNTAX) score was used to assess complex CAD lesions. The renal resistive index (RRI) is a Doppler ultrasound parameter calculated to assess renal haemodynamics. The direct relationship between CAD complexity and RRI was not yet investigated. The aim of our study was to investigate this relationship between RRI and SYNTAX score in stable CAD patients. This study included 214 patients with stable CAD and subsequent coronary angiography done at our institution. Regarding CAD complexity, these patients were classified into 166 patients with low SYNTAX score (SYNTAX 22), and 48 patients with high SYNTAX score (SYNTAX 22). The demographic, laboratory, clinical, echocardiographic data and renal Doppler parameters; including RRI, were recorded. Multivariate logistic regression analysis demonstrated that RRI (odds ratio, OR = 4.440, 95% (confidence interval) CI: 1.418-13.903, p = 0.010) was a novel independent predictor of high SYNTAX score in patients with stable CAD, in addition to other traditional predictors as diabetes mellitus (OR = 4.401, 95% CI: 1.081-17.923, p = 0.04), low-density lipoprotein cholesterol (LDL-C) (OR = 2.957, 95% CI: 1.920-8.995, p = 0.027), multi-vessel CAD (OR = 2.113, 95% CI: 1.241-2.280, p = 0.001) and Gensini score (OR = 6.539, 95% CI: 1.977-21.626, p = 0.002). Receiver operator characteristic curve analysis showed that RRI 0.655 (sensitivity of 80%, specificity of 73.6%) was the best cut-off value for predicting high SYNTAX score. The non-invasively measured RRI is closely associated with high SYNTAX score in stable CAD patients.

The Biomarkers Associated with Unstable Angina Pectoris (UAP)

Objectives: Coronary artery disease (CAD) is the most common form of CVD that begins as stable angina pectoris (SAP) followed by unstable angina pectoris (UAP) and finally critical stage myocardial infarction (MI), which results from rupture of atherosclerotic plaque and a thrombus that blocks the coronary artery supplying the heart, resulted from the death of part of the heart muscle. The underlying cause of coronary artery disease (CAD) is atherosclerosis, which results from the formation of layers of fatty deposits on the inner walls of the arteries. Early diagnosis of MI has an important role in assisting clinicians in prompt planning for its treatment and thus reducing the number of its deaths. Methods: The present study included 20 UAP patients and 20 healthy individuals (controls). In all the cases and controls, levels of cardiac and inflammatory biomarkers were measured by special kits from Hotgen Company via phosphorous technology using UPT-3A converting phosphor immunological analyzer. Results: The levels of both cardiac and inflammatory biomarkers were significantly increased in UAP cases as compared to controls. Also, there was significant positive correlation between cardiac and inflammatory biomarkers in UAP cases. Conclusions: The positive correlation between most cardiac and inflammatory biomarkers in UAP indicates that inflammation occurs in UAP. Hence it is concluded that inflammatory biomarkers (CRP, Hs-CRP and PCT) and cardiac biomarker (cTnI, H-FABP, CK-MB, NT-proBNP and D-dimer) can be markers of UAP and can be used for diagnostic purposes in patients.

Abstract 3114: Time Course Multi-omics Approach Investigating Gene Expression Regulation During Vascular Smooth Muscle Cell Phenotypic Transitioning

Coronary artery disease (CAD) is the leading cause of death in the United States. There is a need for novel therapeutic targets that prevent life-threatening consequences directly associated with plaque accumulation in the vascular wall—the underlying cause of CAD. During the progression of atherosclerosis, vascular smooth muscle cells (VSMCs) transdifferentiate from a contractile to a synthetic phenotype that can either promote fibrous cap stability (fibroblast-like) or contribute to inflammation and plaque accumulation (macrophage or osteoblast-like).The molecular mechanisms driving the functional phenotypic switching of VSMCs are not fully understood and represent a unique opportunity for discovering new treatments directly targeting plaque formation in the vascular wall. We measured gene expression regulation during VSMC dedifferentiation using time-course chromatin remodeling (ATACseq) and nascent transcription data (PROseq). We stimulated VSMCs from three healthy heart transplant donors with PDGF-BB for 0, 4, 8, 12, and 16 hours and performed sequencing in duplicate for each donor at each time point for a total of 30 PROseq and 30 ATACseq libraries. We identified 231,315 regions of accessible chromatin (peaks) in the ATACseq data and 12,954 genes in the PROseq data across the five time points. Likelihood ratio testing detected 13,285 peaks and 7,438 genes with time-dynamic changes in read counts representing six patterns of variable accessibility and nascent transcription following PDGF-BB stimulation: gradual increase/decrease (I/D), immediate I/D, and transient I/D. Transcription factor binding site (TFBS) motif enrichment of dynamic peaks revealed 31 TFs unique to one time dynamic. We identified 157 genes directly downstream of peaks enriched for the 31 TFBSs sharing similar time-specific fold changes. THAP1 binding site motifs had the highest number of cis-regulatory connections (596) and downstream genes (80). Our results capture the first ever time-course ATACseq and PROseq analysis conducted in human VSMCs and provide the ability to predict regulatory edges between TFs and genes in order to map the regulatory cascading events occurring during VSMC switching from a contractile to a synthetic state.

The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy.

Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to block cholesterol synthesis. Many times, additional drugs are also used with this method to lower lipid concentrations in order to achieve certain values of low-density lipoprotein (LDL) cholesterol. Recent advances in photodynamic therapy (PDT) as a new cancer treatment have gained the therapy much attention as a minimally invasive and highly selective method. Photodynamic therapy has been proven more effective than chemotherapy, radiotherapy, and immunotherapy alone in numerous studies. Consequently, photodynamic therapy research has expanded in many fields of medicine due to its increased therapeutic effects and reduced side effects. Currently, PDT is the most commonly used therapy for treating age-related macular degeneration, as well as inflammatory diseases, and skin infections. The effectiveness of photodynamic therapy against a number of pathogens has also been demonstrated in various studies. Also, PDT has been used in the treatment of cardiovascular diseases, such as atherosclerosis and hyperplasia of the arterial intima. This review evaluates the effectiveness and usefulness of photodynamic therapy in cardiovascular diseases. According to the analysis, photodynamic therapy is a promising approach for treating cardiovascular diseases and may lead to new clinical trials and management standards. Our review addresses the used therapeutic strategies and also describes new therapeutic strategies to reduce the cardiovascular burden that is induced by lipids.

Effects of portable pedal machines at work on lipoprotein subfraction profile in sedentary workers – the REMOVE study

BackgroundSedentary behaviour at work is a major cause of atherosclerosis, particularly in tertiary workers. However, no studies have ever assessed the effect of active workstation on lipoprotein subfraction profile. This study aimed to evaluate the effect of 12-week portable pedal machines (PPMs) on lipoprotein subfraction profile among healthy sedentary workers.MethodsHealthy administrative workers were randomized into an intervention group using PPMs for 12 weeks or a control group using normal-desk. Lipoprotein subfractions were assessed using Lipoprint® electrophoresis. Main outcomes were explored using mixed models with sensitivity analyses (four models).ResultsWe included 40 participants (43.7 ± 8.6 years old, 100% women, BMI 23.8 ± 3.4 kg/m2; sedentary time at work 7.7 ± 1.8 h/day). Groups did not differ at baseline in any outcomes. 32 participants finished the trial. Changes in lipoprotein subfractions were especially marked for LDL profile. There was an interaction time x group for all parameters related to LDL and their subfractions: total LDL-cholesterol (p = 0.012), LDL particle size (p = 0.027), large LDL subfractions 1 and 2 (p = 0.001), and small dense LDL subfractions 3 to 7 (p = 0.046), using the crude model. The interaction reflects difference in the direction of changes between groups. The LDL particle size significantly increased in the intervention group (from 271.9 ± 2.5 at t0 to 272.8 ± 1.9 Ångström at t1, p = 0.037) while it did not change in the control group (272.5 ± 1.7 at t0 to 271.8 ± 1.5Å at t1, p = 0.52). All interactions were constantly significant whatever the models. Influencing variables were mainly stress at work that was associated with an increase in total LDL-cholesterol (coefficient 3.15, 95CI 0.20 to 6.11 mg/dl, p = 0.038), and BMI that was associated with Large-LDL, Large-HDL, IDL-C and triglycerides.ConclusionsLipoprotein profile was improved after a 12-week PPMs intervention at work in healthy administrative workers. Changes were mainly showed for LDL and LDL subfractions. Lipoprotein profile was worsened by stress at work, BMI and age.Trial registrationNCT04153214.

Unveiling Atherosclerotic Plaque Heterogeneity and SPP1+/VCAN+ Macrophage Subtype Prognostic Significance Through Integrative Single-Cell and Bulk-Seq Analysis.

Dysregulated macrophages are important causes of Atherosclerosis (AS) formation and increased plaque instability, but the heterogeneity of these plaques and the role of macrophage subtypes in plaque instability have yet to be clarified. This study integrates single-cell and bulk-seq data to analyze atherosclerotic plaques. Unsupervised clustering was used to reveal distinct plaque subtypes, while survival analysis and gene set variation analysis (GSVA) methods helped in understanding their clinical outcomes. Enrichment of differential expression of macrophage genes (DEMGs) score and pseudo-trajectory analysis were utilized to explore the biological functions and differentiation stages of macrophage subtypes in AS progression. Additionally, CellChat and the BayesPrism deconvolution method were used to elucidate macrophage subtype interaction and their prognostic significance at single-cell resolution. Finally, the expression of biomarkers was validated in mouse experiments. Three distinct AS plaque subtypes were identified, with cluster 3 plaque subtype being particularly associated with higher immune infiltration and poorer prognosis. The DEMGs score exhibited a significant elevation in three macrophage subtypes (SPP1+/VCAN+ macrophages, IL1B+ macrophages, and FLT3LG+ macrophages), associated with cluster 3 plaque subtype and highlighted the prognostic significance of these subtypes. Activation trajectory of the macrophage subtypes is divided into three states (Pre-branch, Cell fate 1, and Cell fate 2), and Cell fate 2 (SPP1+/VCAN+ macrophages, IL1B+ macrophages, and FLT3LG+ macrophages dominant) exhibiting the highest DEMGs score, distinct interactions with other cell components, and relating to poorer prognosis of ischemic events. This study also uncovered a unique SPP1+/VCAN+ macrophage subtype, rare in quantity but significant in influencing AS progression. Machine learning algorithms identified 10 biomarkers crucial for AS diagnosis. The validation of these biomarkers was performed using Mendelian Randomization analysis and in vitro methods, supporting their relevance in AS pathology. Our study provides a comprehensive view of AS plaque heterogeneity and the prognostic significance of macrophage subtypes in plaque instability.

MicroRNA-mediated Regulation of LDL Receptor: Biological and Pharmacological Implications.

One of the main causes of atherosclerosis is a disruption in cellular cholesterol hemostasis. The low-density lipoprotein receptor (LDLR) is an important factor in maintaining cholesterol homeostasis by the receptor-mediated endocytosis of LDL particles. Defective hepatic LDLR activity and uptake of LDL particles lead to elevated blood levels of low-density lipoprotein cholesterol (LDL-C), which is associated with a higher risk of atherosclerotic cardiovascular disease. LDLR expression can be affected by microRNAs (miRNAs). Some miRNAs, like miR-148a, miR-185, miR-224, miR-520, miR-128-1, miR-27a/b, miR-130b, and miR-301 seem to be important post-transcriptional regulators of LDLR related genes. These findings indicate the critical role of miRNAs in regulating LDL metabolism. The aim of this review was to provide insight into the miRNAs involved in LDLR activity and their potential roles in the treatment of cardiovascular disease.

Abstract P113: Associations of Immune Cell Subsets With Coronary Artery Calcium Incidence and Progression in the Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium (CAC) and its progression strongly associates with incident cardiovascular disease (CVD). Although immune dysregulation and related inflammation are important causes of coronary artery disease, few data exist on associations between specific immune cell subsets and CAC presence and progression. Hypothesis: We hypothesized innate &amp; adaptive immune cell subsets are associated with longitudinal CAC changes Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we examined associations of immune cell subsets (measured at baseline in peripheral blood by flow cytometry) with incident CAC and CAC progression. Of 975 participants sampled who had CAC and immune cell subsets measured at baseline (2000-02), 378 had CAC 0 at baseline and were used to examine incident CAC from MESA exam 2 (2002-04) through 5 (2010-12); the remaining 597 participants were included to analyze CAC progression from exam 1-5. Incident CAC analyses (N=378) used Weighted Cox regressions to determine hazard ratios of incident CAC, adjusted for age, gender, race, MESA site, education, smoking status, blood pressure, body-mass index, diabetes status, cholesterol, HDL cholesterol, statin use, and antihypertensive medication. CAC progression analyses among individuals with nonzero CAC at baseline (N=597) used weighted multivariable-adjusted linear mixed models to investigate associations of baseline immune cell subsets with CAC progression, with Benjamini-Hochberg correction for multiple comparisons. Results: Among 378 participants with CAC 0 and immune cell subsets measured at baseline, 149 had incident CAC between MESA examination 2-5. Of 19 subsets measured, natural killer (NK) cells (CD3-CD16+CD56+) were associated with an elevated risk of incident CAC (hazard ratio (HR) 1.26 per standard deviation (SD) higher NK cells; 95% confidence interval (CI) 1.03-1.56, p=0.03). Two CD4+ T cell subsets, Th1 (HR 0.81, 95% CI 0.66-0.99, p=0.04) and Th2 (HR 0.80, 95% CI 0.64-0.99, p=0.04) were associated with a borderline lower risk for incident CAC. In analyses of CAC progression for participants with nonzero CAC at baseline (N=597), CD19+ B-cells were associated with CAC progression (beta-coefficient=53.1 Agatston units per SD higher B-cells proportion, 95% CI 2.0-104.2, p=0.04), while intermediate monocytes (CD14+CD16+) (beta = -71.6 Agatston units per SD higher, 95% CI -134.9 - -8.3, p=0.03) and higher T-regulatory cells (CD4+CD25+CD127-) (beta = -71.6 Agatston units per SD higher, 95% CI -119.1 - -4.8, p=0.03) were negatively associated with CAC progression. Conclusions: Among individuals with CAC 0 at baseline, NK cells were associated with incident CAC. In individuals with nonzero CAC at baseline, T-regulatory cells and intermediate monocytes were negatively associated with CAC progression, whereas B-cells were positively associated with CAC progression.

TLN1 synergizes with ITGA5 to ameliorate cardiac microvascular endothelial cell dysfunction.

The complex process of atherosclerosis is thought to begin with endothelial cell dysfunction, and advanced atherosclerosis is the underlying cause of coronary artery disease (CAD). Uncovering the underlying mechanisms of CAD-related endothelial cell injury may contribute to the treatment. Cardiac microvascular endothelial cells (CMVECs) were treated with oxidised low-density lipoprotein (ox-LDL) to mimic an injury model. The involvement of Talin-1 (TLN1) and integrin alpha 5 (ITGA5) in the proliferation, apoptosis, angiogenesis, inflammatory response, and oxidative stress in CMVECs were assessed. TLN1 overexpression assisted CMVECs in resistance to ox-LDL stimulation, with alleviated cell proliferation and angiogenesis, reduced apoptosis, inflammatory response, and oxidative stress. TLN1 overexpression triggered increased ITGA5, and ITGA5 knockdown reversed the effects of TLN1 overexpression on the abovementioned aspects. Together, TLN1 synergized with ITGA5 to ameliorate the dysfunction in CMVECs. This finding suggests their probable involvement in CAD, and increasing their levels is beneficial to disease relief.

A Study of transcription factor MEF2A gene polymorphisms in patients with coronary artery disease.

MEF2A (myocyte enhancer factor-2A) is a transcription factor of the MEF2 family. It has been recognized as the cause of coronary artery disease in the absence of any other clinical characteristic. It is involved in vascular development and is most commonly found in the coronary artery endothelium. The goal of this case-control study was to see if there was a link between polymorphisms in the MEF2A gene and coronary artery disease. A case-control study was carried out to look into the possible significance of MEF2A polymorphisms as a risk factor for coronary artery disease. This research included 225 patients and 225 healthy controls. A biochemical examination was carried out to evaluate the risk factors for developing this condition. The polymorphisms of Mef2A (1250 C > T in exon 8 and 452 G > T, 481 A > G in exon 11) were found using the PCR-RFLP technique. All identified risk variables, such as hypercholesterolemia, diabetes mellitus, and hypertriglyceridemia, were shown to be statistically significant in the current study for coronary artery disease occurrence. The most polymorphisms were found in MEF2A 1250 C > T, MEF2A 452 G > T, and MEF2A 481 A > G. The genotyping results for MEF2A 1250, MEF2A 452, and MEF2A 481 were (X2 = 2.985; P = 0.235), (X2 = 4.371; P = 0.112), and (X2 = 4.025; P = 0.134), respectively. In conclusion, we identified a much higher incidence of MEF2A in people with coronary artery disease, and MEF2A may play a crucial role in cardiovascular pathophysiology. Patients and controls had considerably different genetics and frequency of alleles.