Plaque Formation Research Articles

In vitro drug release profiling of Sirolimus polymeric microparticles coated long-acting stents

In the realm of arterial disease interventions, drug-eluting stents (DES) have become a vital therapeutic choice in preventing atherosclerotic plaque formation and restenosis and facilitating vessel healing. Sirolimus-encapsulated poly Lactic-co-Glycolic acid (PLGA) Microparticles (MPs) were developed using solvent evaporation. MPs were freeze-dried with a cryoprotectant and coated on the stent surface using an efficient and reproducible nitrogen-assisted spray coating technique. The MPs displayed a uniform distribution particle size of 4.38 ± 1.1 μm, span value of 0.88 ± 0.02, coating mass transfer efficiency of 13.45 ± 1.1 % on the stent, and a coating time of ≤ 2 min per stent. Post sterilization, the particle size and morphology of the coated stents remained unchanged. Accelerated in vitro drug release profiles were evaluated under different conditions, indicating significant influences based on dissolution methods ranging from 28.2 %±4.3 %, 42.5 %±5.3 %, 76.6 %±4.7 %, and 84.25 %±3.1 % for dialysis bag (DB), vessel simulating flow-through cell (vFTC), flow-through cell (FTC), and sample and separate (SS) technique respectively for 48 h. The drug release mechanism from the coated stents is governed by the combination of the Korsmeyer Peppas and Higuchi models. The developed dissolution method exhibited discriminative effectiveness when evaluated with critical formulation attributes and process parameter variations. The 48 h accelerated drug release studies correlated well with the 6-month real-time release rate with an R2 value of 0.9142 and Pearson’s R2 of 0.9561. Ex-vivo studies demonstrated the permeation of MPs into artery tissues. Stability studies confirmed that MPs coated stents maintained desired properties at 4 °C and 30 °C/65 % RH for 6 months. Overall, these findings contribute to advancing stent technology, suggesting the potential for improvement of arterial interventions and enhanced patient outcomes.

Investigating the impact of doxorubicin on plaque formation in an apolipoprotein-E-deficient mouse model of atherosclerosis

Investigating the impact of doxorubicin on plaque formation in an apolipoprotein-E-deficient mouse model of atherosclerosis

Are Hair Scalp Trace Elements Correlated with Atherosclerosis Location in Coronary Artery Disease?

Coronary artery disease is among the leading current epidemiological challenges. The genetic, clinical, and lifestyle-related risk factors are well documented. The reason for specific epicardial artery locations remains unsolved. The coronary artery topography and blood flow characteristics may induce local inflammatory activation. The atherosclerotic plaque formation is believed to represent inflammatory response involving enzymatic processes co-factored by trace elements. The possible relation between trace elements and coronary artery disease location was the subject of the study. There were 175 patients (107 (61) men and 68 (39) females) in a median (Q1-3) age of 71years (65-76) admitted for coronary angiography due to chronic coronary syndrome. The angiographic results focused on the percentage of lumen stenosis in certain arteries and were compared with the results for hair scalp trace elements. The correlation between left main coronary artery atherosclerotic plaques and nickel (Ni), zinc (Zn), and antimony (Sb) hair scalp concentration was noted. The analysis revealed a positive relation between left descending artery disease and chromium (Cr), sodium (Na), arsenic (As), and molybdenum (Mo) and a negative correlation with strontium (Sr). The atherosclerotic lesion in the circumflex artery revealed correlations in our analysis with sodium (Na), potassium (K), chromium (Cr), nickel (Ni), arsenic (As), and negative with strontium (Sr) (r) hair scalp concentrations. The negative correlations between right coronary artery disease and magnesium (Mg) and strontium (Sr) concentrations were noted. The possible explanation of different epicardial artery involvement and severity by atherosclerotic processes may lay in their topography and blood rheological characteristics that induce different inflammatory reactions co0factored by specific trace elements. The trace element concentration in the hair scalp may correlate with a particular coronary atherosclerotic involvement, including the severity of lumen reduction. This may indicate the missing link between the pathophysiological processes of atherosclerosis development and its location in coronary arteries.

Restoration of miR-299-3p promotes efferocytosis and ameliorates atherosclerosis via repressing CD47 in mice.

Atherosclerotic plaque formation is largely attributed to the impaired efferocytosis, which is known to be associated with the pathologic upregulation of cluster of differentiation 47 (CD47), a key antiphagocytic molecule. By gene expression omnibus (GEO) datasets analysis, we identified that four miRNAs are aberrantly downregulated in atherosclerosis, coronary artery disease, and obesity. Of them, hsa-miR-299-3p (miR-299-3p) was predicted to target the 3'UTR of human CD47 mRNA by bioinformatics analysis. Further, we demonstrated that miR-299-3p negatively regulates CD47 expression by binding to the target sequence "CCCACAU" in the 3'UTR of CD47 mRNA through luciferase reporter assay and site-directed mutagenesis. Additionally, we found that miR-299-3p was downregulated by ~32% in foam cells in response to oxidized low-density lipoprotein (ox-LDL) stimulation, thus upregulating CD47 and contributing to the impaired efferocytosis. Whereas, restoration of miR-299-3p reversed the ox-LDL-induced upregulation of CD47, thereby facilitating efferocytosis. In high-fat diet (HFD) fed ApoE-/- mice, we discovered that miR-299-3p was downregulated thus leading to upregulation of CD47 in abdominal aorta. Conversely, miR-299-3p restoration potently suppressed HFD-induced upregulation of CD47 and promoted phagocytosis of foam cells by macrophages in atherosclerotic plaques, thereby reducing necrotic core, increasing plaque stability, and mitigating atherosclerosis. Conclusively, we identify miR-299-3p as a negative regulator of CD47, and reveal a molecular mechanism whereby the ox-LDL-induced downregulation of miR-299-3p leads to the upregulation of CD47 in foam cells thus contributing to the impaired efferocytosis in atherosclerosis, and propose miR-299-3p can potentially serve as an inhibitor of CD47 to promote efferocytosis and ameliorate atherosclerosis.

The role of LDL-cholesterol increment in carotid artery plaques formation among familial hypercholesterolemia patients population

The role of LDL-cholesterol increment in carotid artery plaques formation among familial hypercholesterolemia patients population

Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview.

This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer's, multiple sclerosis, and Parkinson's through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori's role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment.

Reactive Oxygen Species-Responsive Nanoparticle Delivery of Small Interfering Ribonucleic Acid Targeting Olfactory Receptor 2 for Atherosclerosis Theranostics.

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by arterial intimal lipid plaques. Small interfering ribonucleic acid (siRNA)-based therapies, with their ability to suppress specific genes with high targeting precision and minimal side effects, have shown great potential for AS treatment. However, targets of siRNA therapies based on macrophages for AS treatment are still limited. Olfactory receptor 2 (Olfr2), a potential target for plaque formation, was discovered recently. Herein, anti-Olfr2 siRNA (si-Olfr2) targeting macrophages was designed, and the theranostic platform encapsulating si-Olfr2 to target macrophages within atherosclerotic lesions was also developed, with the aim of downregulating Olfr2, as well as diagnosing AS through photoacoustic imaging (PAI) in the second near-infrared (NIR-II) window with high resolution. By utilization of a reactive oxygen species (ROS)-responsive nanocarrier system, the expression of Olfr2 on macrophages within atherosclerotic plaques was effectively downregulated, leading to the inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 β (IL-1β) secretion, thereby reducing the formation of atherosclerotic plaques. As manifested by decreased Olfr2 expression, the lesions exhibited a significantly alleviated inflammatory response that led to reduced lipid deposition, macrophage apoptosis, and a noticeable decrease in the necrotic areas. This study provides a proof of concept for evaluating the theranostic nanoplatform to specifically deliver si-Olfr2 to lesional macrophages for AS diagnosis and treatment.

A Comprehensive Guide to Aortic Atheroma: Delving in Its Causes, Detection, and Treatment.

Aortic atheroma, a common disease, is characterized by the formation and accumulation of atheromatous plaques within the aorta. The disease manifestations range from asymptomatic conditions to life-threatening complications like stroke or aortic dissection. The severity of this condition necessitates a detailed look at its pathophysiology, diagnostics, and management options. This guide provides a detailed overview of aortic atheroma, its definition, worldwide occurrence, demographic patterns, and underlying pathophysiology. It also elucidates the symptomatology associated with atheromatous changes in the aorta, diagnostic criteria for identifying the disease, and the latest epidemiological data. This article presents current treatment modalities, focusing on preventive and lifestyle approaches to cease further progression of atheromatous disease. It additionally reviews relevant case studies to give practical insights into the challenges faced and consequences of managing aortic atheroma. The in-depth discussion of aortic atheroma improves the perspective to a broader public health relevance, giving importance to the need for continuous improvement in medical practices, and personalized healthcare strategies to reduce risk and better patient outcomes.

Association of serum 25-hydroxyvitamin D3 levels with carotid artery intima-media thickness and carotid atherosclerotic plaques in smokers

ObjectiveThis study explores the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels with carotid artery intima-media thickness (CIMT), and the presence of carotid atherosclerotic plaques in individuals with a history of smoking. MethodsA total of 469 patients suspected of having carotid atherosclerosis, aged 52 to 73 years with an average age of 65.26 ± 4.37 years, were recruited from the author's hospital from January 2023 to October 2023. All patients had a smoking history of nearly 5 years. Based on their serum 25(OH)D3 levels, they were divided into two groups: the normal group (serum level 30–50 ng/mL, n = 300) and the deficiency group (<30 ng/mL, n = 169). General details of the two patient groups were collected. Carotid artery ultrasound was employed to assess pulse wave velocity (PWV), carotid artery compliance coefficient (CC), and CIMT. Blood chemistry analysis measured serum lipid metabolism indicators including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HD-LC). The relationship between CIMT and each variable was analyzed through Pearson correlation, and logistic regression was used to identify risk factors influencing carotid artery plaque development. ResultsGeneral patient information between the two groups showed no significant differences (P > 0.05). Patients in the 25(OH)D3 deficiency group exhibited elevated left and right PWV and CC compared to the 25(OH)D3 normal group (P < 0.05). The deficiency group exhibited larger CIMT and plaque area compared to the normal group (P < 0.05). Additionally, the deficiency group demonstrated higher levels of TC, LDL-C, and HD-LC compared to the normal group (P < 0.05). A moderate positive correlation was found between TC, LDL-C, and CIMT (P < 0.05), while a strong positive correlation existed between 25(OH)D3 and CIMT (P < 0.05). In smokers, the formation of carotid artery plaque was associated with factors such as patient age, CIMT, serum LDL-C, and 25(OH)D3 levels (P < 0.05). As age, CIMT, LDL-C levels increased, and 25(OH)D3 levels decreased, the risk of carotid plaques in smokers increased (P < 0.05). ConclusionsSmokers with lower 25(OH)D3 levels exhibit higher CIMT and more prominent carotid atherosclerotic plaques, indicating increased arterial stiffness and elevated cardiovascular risk. These findings demonstrate crucial implications that insufficient levels of vitamin D may potentially contribute to a higher risk of atherosclerosis among smokers.

Synthesis and mechanistic study of Aβ42 C-terminus domain derived tetrapeptides that inhibit Alzheimer’s Aβ-aggregation-induced neurotoxicity

Amyloid plaque formation in the brain is mainly responsible for the onset of Alzheimer’s disease (AD). Structure-based peptides have gained importance in recent years, and rational design of the peptide sequences for the prevention of Aβ-aggregation and related toxicity is imperative. In this study, we investigate the structural modification of tetrapeptides derived from the hydrophobic C-terminal region of Aβ42 “VVIA-NH2” and its retro-sequence “AIVV-NH2.” A preliminary screening of synthesized peptides through an MTT cell viability assay followed by a ThT fluorescence assay revealed a peptide 13 (Ala-Ile-Aib-Val-NH2) that showed protection against Aβ-aggregation and associated neurotoxicity. The presence of the α-helix inducer “Aib” in peptide 13 manifested the conformational transition from cross-β-sheets to α-helical content in Aβ42. The absence of fibrils in electron microscopic analysis suggested the inhibitory potential of peptide 13. The HRMS, DLS, and ANS studies further confirmed the inhibitory activity of 13, and no cytotoxicity was observed. The structure-based peptide described herein is a promising amyloid-β inhibitor and provides a new lead for the development of AD therapeutics.

The calcium-sensing-receptor (CaSR) in adipocytes contributes to sex-differences in the susceptibility to high fat diet induced obesity and atherosclerosis

Female mice are more resistant to obesogenic effects of a high-fat diet (HFD), compared to male mice. Although the underlying mechanisms are poorly understood, sex hormones seem to play an important role. Interestingly, the activity of the oestrogen receptor-α (ERα) is affected by the calcium-sensing-receptor (CaSR). Therefore, we investigated sex-differences upon diet-induced obesity and the role of adipocyte-specific CaSR herein. Adipocyte-specific Casr deficient mice (AdipoqCre+Casrflox) and control mice (Casrflox) were injected with AAV8-PCSK9 to make them prone to develop atherosclerosis and fed an obesity-inducing diet for 12 weeks. Female mice have lower visceral white adipose tissue (vWAT) mass compared to male mice, while this sex-difference is abolished upon adipocyte-specific Casr deficiency. Furthermore, while females showed elevated levels of inflammatory cytokines and CD3+CD8+ T cell accumulation in vWAT, compared to males, adipocyte-specific Casr deficiency abrogated this sex-phenotype and demonstrated an inhibition of inflammatory signalling pathways. The expression of Erα, as well as associated genes involved in adipocyte differentiation, was increased in female mice in a mostly adipocyte-specific Casr dependent manner. Interestingly, circulating lipid levels were reduced in female compared to male mice, which correlated with decreased atherosclerotic plaque formation. These systemic effects were abrogated upon adipocyte-specific Casr deficiency. Our findings indicate that female mice show a more pronounced vWAT dysfunction compared to males upon obesity. This sex effect is abolished upon adipocyte-specific Casr deficiency. In contrast, females show diminished atherosclerotic plaque formation compared to males, an effect that was abrogated by adipocyte-specific Casr deficiency. This work was supported by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, by the Corona Foundation, by the Deutsche Forschungsgemeinschaft (DFG), the BMBF and Free State of Bavaria and the DZHK.

Antiviral Effect of Microalgae Phaeodactylum tricornutum Protein Hydrolysates against Dengue Virus Serotype 2.

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 μg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.

Injectable agents for the induction of Peyronie's disease in model rats: a comparative study.

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.

Plasma Somatostatin Levels Are Lower in Patients with Coronary Stenosis and Significantly Increase after Stent Implantation.

Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality. Inflammation is the key pathophysiological process responsible for the formation, progression, instability, and healing of atherosclerotic plaques. Methods: We measured SST-like immunoreactivity (SST-LI) in the plasma of healthy volunteers in different age groups and also that of stable angina patients with coronary heart disease (CHD) using ELISA and tracked changes during invasive coronary interventions (coronarography) with and without stent implantation. Samples were collected at (1) pre-intervention, (2) after coronarography, (3) 2 h after coronarography initiation and coronary stent placement, and (4) the next morning. Results: There was a strong negative correlation between SST-LI concentrations and age; the plasma SST-LI of older healthy volunteers (47-73 years) was significantly lower than in young ones (24-27 years). Baseline SST-LI in CHD patients who needed stents was significantly reduced compared to those not requiring stents. Plasma SST-LI significantly increased two hours post stent insertion and the next morning compared to pre-intervention levels. Conclusions: Age-related SST decrease might be a consequence of lower gene expression within specific hypo-thalamic nuclei as has been previously demonstrated in rodent animals. Reperfusion of ischemic myocardium post-stent implantation may trigger SST release, potentially offering protective benefits in coronary heart disease. Investigating this SST-mediated mechanism could offer valuable insights for future therapies.

Targeting the tyrosine kinase Src in endothelium attenuates inflammation and atherogenesis induced by disturbed flow.

Previous studies have shown that Src can regulate inflammation and tumour progression. However, the mechanisms by which Src regulates the inflammatory response of vascular endothelium and atherogenesis are currently poorly understood. This study aimed to investigate the role of Src in endothelial inflammation and atherogenesis, as well as the underlying mechanisms. Real-time quantitative PCR was used to measure the mRNA levels of inflammatory genes. The phosphorylation and localization of proteins were examined using western blotting and immunofluorescence, respectively. The level of p-Src Y416 in mouse endothelium was directly determined using en face staining. Endothelial-specific knockdown of Src was achieved by tail vein injection of AAV-sgSrc in ApoE-/-; Cas9LSL/LSL; Cdh5-cre mice. Atherosclerosis was induced by partial ligation of the carotid artery. Oscillatory shear stress (OSS) promotes the phosphorylation of Src at Y416 in endothelial cells, and Piezo1 is required for this regulatory process. Overexpression of constitutively active Src promotes endothelial inflammation, as well as phosphorylation of Stat3 (at Y705) and its nuclear translocation. Endothelial inflammation induced by OSS was abolished by the Src inhibitor dasatinib or si-Src. Dasatinib, when administered orally, reduced endothelial inflammation and plaque formation in ApoE-/- mice induced by partial carotid artery ligation. Additionally, plaque formation was decreased in the ligated left carotid artery of mice with endothelial-specific Src knockdown. Disturbed flow promotes endothelial inflammation and atherogenesis through the Piezo1-Src-Stat3 pathway. Therefore, inhibiting Src in endothelial cells could be a promising therapeutic strategy to treat atherogenesis.

Structure of a model lipid membrane oxidized by human 15-lipoxygenase-2

Enzyme-mediated lipid oxidation is an important regulatory event in cell signaling, with oxidized lipids being potent signaling molecules that can illicit dramatic changes in cell behavior. For example, peroxidation of an arachidonoyl poly-unsaturated fatty acid by the human enzyme 15-lipoxygenase-2 (15-LOX-2) has been associated with formation of atherosclerotic plaques. Previous work on synthetically oxidized membranes has shown that oxidized lipid tails will change their conformation to facilitate interactions between the peroxide group and the lipid headgroups. However, this phenomenon has not been directly observed for a lipid membrane that has undergone enzyme-catalyzed oxidation. In this study, we report on the structure of a model lipid membrane before and after oxidation by 15-LOX-2. A model lipid membrane monolayer at the air-liquid interface was constructed from 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (SAPC) in a Langmuir trough, and X-ray reflectivity measurements were conducted to determine the electron density profile of the system. Exposure to 15-LOX-2 caused a dramatic change in the SAPC structure, namely a blurred distinction between the lipid tail/head layers and shortening of the average lipid tail length by ∼3 Å. The electron density profile of the oxidized SAPC monolayer is similar to that of a synthetically oxidized substrate mimic. Overall, this reported observation of an enzymatically-oxidized membrane structure in situ is helping to bridge a gap in the literature between structural studies on synthetically oxidized membranes and cellular studies aiming to understand physiological responses.

Omics Science and Social Aspects in Detecting Biomarkers for Diagnosis, Risk Prediction, and Outcomes of Carotid Stenosis.

Carotid stenosis is characterized by the progressive narrowing of the carotid arteries due to the formation of atherosclerotic plaque, which can lead to stroke and death as major complications. Numerous biomarkers allow for its study and characterization, particularly those related to "omics" sciences. Through the most common research databases, we report representative studies about carotid stenosis biomarkers based on genomics, transcriptomics, proteomics, and metabolomics in a narrative review. To establish a priority among studies based on their internal validity, we used a quality assessment tool, the Scale for the Assessment of Narrative Review Articles (SANRA). Genes, transcriptomes, proteins, and metabolites can diagnose the disease, define plaque connotations, predict consequences after revascularization interventions, and associate carotid stenosis with other patient comorbidities. It also emerged that many aspects determining the patient's psychological and social sphere are implicated in carotid disease. In conclusion, when taking the multidisciplinary approach that combines human sciences with biological sciences, it is possible to comprehensively define a patient's health and thus improve their clinical management through precision medicine.

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis

BackgroundJuvenile dermatomyositis (JDM) is a systemic vasculopathy associated with metabolic derangements and possible increased risk for premature atherosclerosis. Oxidation of low-density lipoprotein (LDL) in the endothelium is an early step in atherosclerotic plaque formation. It is not known if oxidized LDL is altered in children with untreated JDM. The deposition of oxidized LDL in the vasculature of muscle biopsies (MBx) from patients with untreated JDM and pediatric controls was assessed.FindingsFrozen tissue sections of MRI-directed MBx from 20 female children with untreated JDM and 5 female controls were stained with DAPI and fluorescently labeled antibodies against von Willebrand factor (vWF) and LDL oxidized by copper (oxLDL). Blood vessels were identified by positive vWF staining, and total fluorescence of oxLDL within the vessel walls was measured. Children with untreated JDM had increased deposition of oxLDL in the walls of muscle vasculature compared to healthy children (difference in means ± SEM = 19.86 ± 8.195, p = 0.03). Within the JDM cohort, there was a trend towards increased oxLDL deposition with longer duration of untreated disease (r = 0.43, p = 0.06). There was no significant correlation found between oxLDL deposition and markers of acute JDM disease activity including disease activity scores or muscle enzymes.ConclusionsThis study found increased deposition of oxLDL within blood vessels of children with untreated JDM supporting the concern that these children are at increased risk for premature atherosclerosis from chronic exposure to vascular oxLDL. This study highlights the importance of early diagnosis and treatment initiation to ameliorate cardiovascular damage.

The Relevance of Phytate for the Treatment of Chronic Kidney Disease.

Diets high in plant-based foods are commonly recommended for people with chronic kidney disease (CKD). One putative advantage of these diets is reduced intestinal phosphate absorption. This effect has been ascribed to phytic acid (myoinositol hexaphosphoric acid) and its anion, phytate, that are present in many plant foods, particularly in the seeds, nuts, grains and fruits of plants. This paper reviews the structure and many actions of phytate with particular reference to its potential effects on people with CKD. Phytate binds avidly to and can reduce gastrointestinal absorption of the phosphate anion and many macrominerals and trace elements including iron, zinc, calcium and magnesium. This has led some opinion leaders to label phytate as an "anti-nutrient." The human intestine lacks phytase; hence, phytate is essentially not degraded in the small intestine. A small amount of phytate is absorbed from the small intestine, although phytate bound to phosphate is poorly absorbed. Clinical trials in maintenance hemodialysis patients indicate that intravenously administered phytate may decrease hydroxyapatite formation, vascular calcification and calciphylaxis. Orally administered phytate or in vitro studies indicate that phytate may also reduce osteoporosis, urinary calcium calculi formation and dental plaque formation. Phytate appears to have anti-inflammatory and antioxidant effects, at least partly due to its ability to chelate iron. Other potential therapeutic roles for phytate, not definitively established, include suppression of cancer formation, reduction in cognitive decline that occurs with aging, and amelioration of certain neurodegenerative diseases and several gastrointestinal and metabolic disorders. These latter potential benefits of phytate are supported by cell or animal research or observational studies in humans. Many of the above disorders are particularly common in CKD patients. Definitive clinical trials to identify potential therapeutic benefits of phytate in CKD patients are clearly warranted.

Involvement of Expression of miR33-5p and ABCA1 in Human Peripheral Blood Mononuclear Cells in Coronary Artery Disease.

MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting ABCA1 can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting ABCA1 in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL's cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p (p = 0.027) and ABCA1 (p = 0.003) expression levels were higher in CAD patients, while miR-33a-5p (p < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of ABCA1 were linked to a lower CAD risk. Atorvastatin upregulated ABCA1 mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased ABCA1 expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and ABCA1, suggesting potential therapeutic strategies for CAD prognosis and treatment.