Search Results (333)

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Background/Objetives: Sea lice (Caligus rogercresseyi) pose a major threat to Atlantic salmon (Salmo salar) aquaculture by compromising fish health and reducing production efficiency. While genetic variation in parasite load has been reported, the molecular mechanisms underlying this variation remain unclear. Methods: two sea lice challenge trials were conducted, achieving high infestation rates (47.5% and 43.5%). A total of 85 fish, selected based on extreme phenotypes for lice burden (42 low, 43 high), were subjected to transcriptomic analysis. Differential gene expression was integrated with allele-specific expression (ASE) analysis to uncover cis-regulatory variation influencing host response. Results: Sixty genes showed significant ASE (p < 0.05), including 33 overexpressed and 27 underexpressed. Overexpressed ASE genes included Keratin 15, Collagen IV/V, TRIM16, and Angiopoietin-1-like, which are associated with epithelial integrity, immune response, and tissue remodeling. Underexpressed ASE genes such as SOCS3, CSF3R, and Neutrophil cytosolic factor suggest individual variation in cytokine signaling and oxidative stress pathways. Conclusions: several ASE genes co-localized with previously identified QTLs for sea lice resistance, indicating that cis-regulatory variants contribute to phenotypic differences in parasite susceptibility. These results highlight ASE analysis as a powerful tool to identify functional regulatory elements and provide valuable candidates for selective breeding and genomic improvement strategies in aquaculture. Full article

Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that was discovered in 2000 by three independent laboratories. In the ensuing two and a half decades, extensive work has been conducted to determine its physiological and pathological functions. ANGPTL4 has been shown to be involved in many biological processes, including glucose and lipid metabolism, angiogenesis, and wound healing, with implications in diseases such as type 2 diabetes, cardiovascular (e.g., atherosclerosis) and renal diseases, and cancer. For instance, ANGPTL4 is upregulated in several cancers, including renal cell carcinoma, breast cancer, and colorectal cancer. Interestingly, ANGPTL4 has been shown to exhibit both pro-tumor—promoting tumor growth, cell survival, angiogenesis and metastasis—as well as anti-tumor activities, underscoring its complex roles in cancer biology. This review examines the comprehensive biological functions of ANGPTL4 and its contributions to disease mechanisms with a specific emphasis on cancer, as well as its potential as a therapeutic target across different types of human cancers. Full article

Background: Crohn’s disease (CD) is a chronic disease perpetuated through key pro-inflammatory molecules, including tumor necrosis factor-alpha (TNFα). Angiopoietin-like protein 8 (ANGPTL8) may contribute to inflammation cascades. This study aimed to investigate how ANGPTL8 levels are influenced in patients with CD prior to and following anti-TNF therapy. Methods: Patients were divided into 3 groups. Patients with CD in clinical remission receiving IFX for at least 24 weeks (IFX-experienced group), patients scheduled to start IFX (IFX-naïve group), and healthy controls (control group). In the IFX-experienced group, ANGPTL8 levels were measured 24 h before the next maintenance IFX dose. In the IFX-naïve group, levels were measured at week 0 and week 24, and in the control group, they were measured randomly. Results: The total number of participants was 166. The numbers of IFX-experienced, IFX-naïve patients, and healthy controls were 82, 13, and 71, respectively. Mean age ranged from 27 to 33 years of age across the three groups. Eighty-four (51%) participants were female. ANGPTL8 levels were significantly higher in patients with CD (138.26 ± 8.47 pmol) compared to the healthy control group (102.52 ± 5.99 pmol, p = 0.001). Among IFX-naïve patients receiving anti-TNFα treatment, ANGPTL8 levels decreased significantly from 145.06 ± 17.93 pmol pre-treatment (week 0) to 81.78 ± 10.61 pmol post-treatment (week 24), p = 0.007. Conclusions: Our findings suggest that ANGPTL8 levels are elevated in CD and may be involved in the inflammatory process. The marked reduction in ANGPTL8 levels following anti-TNFα treatment indicates its potential as a biomarker for treatment response. Further research should focus on the exact mechanisms through which ANGPTL8 influences CD progression and its utility in clinical practice. Full article

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) supports critically ill patients with respiratory failure. However, ECMO may induce systemic inflammation, hemolysis, and hemodilution, potentially resulting in endothelial activation and damage. Therefore, this study explored the longitudinal changes in circulating markers of inflammation, hemolysis, and endothelial activation and damage in patients with COVID-19 on VV-ECMO. Methods Plasma was obtained before, within 48 h as well as on day 4, week 1, and week 2 of ECMO support and after decannulation. Circulating markers were measured using Luminex, ELISA, and spectrophotometry. Human pulmonary endothelial cells were exposed to patient plasma, and in vitro endothelial permeability was assessed using electric cell-substrate impedance sensing. Results From April 2020 to January 2022, plasma was collected from 14 patients (71.4% male; age 54 (45–61) years). IL-6 levels decreased (1.238 vs. 0.614 ng/mL, p = 0.039) while ICAM-1 increased (667 vs. 884 ng/mL, p = 0.003) over time when compared to pre-ECMO. Angiopoietin-1 decreased after ECMO initiation (7.57 vs. 3.58 ng/mL, p = 0.030), whereas angiopoietin-2 increased (5.20 vs. 10.19 ng/mL, p = 0.017), particularly in non-survivors of ECMO. Cell-free hemoglobin decreased directly after VV-ECMO initiation but remained stable thereafter (55.29 vs. 9.19 mg/dL, p = 0.017). Moreover, the plasma obtained at several time points during the ECMO run induced in vitro pulmonary endothelial hyperpermeability. Conclusions This exploratory study shows that patients on VV-ECMO support due to COVID-ARDS exhibit progressive endothelial activation and damage but not inflammation and hemolysis. Larger prospective studies are necessary to elucidate pathophysiological pathways leading to endothelial activation and damage, thereby reducing organ failure in these critically ill patients. Full article

Previous research has linked both endothelial protein changes and vitamin D with infertility. This study was undertaken to investigate the association of proteins associated with endothelial function and vitamin D status in the luteal phase at day 21 in a group of non-obese women prior to in vitro fertilization (IVF) with either unexplained infertility (UI) or male factor infertility (MFI). Twenty-five non-obese Caucasian women from a UK academic center with MFI (n = 14) and UI (n = 11) were recruited. Blood was withdrawn at day 21 of the menstrual cycle at the time of mock embryo transfer. Vitamin D parameters were measured by tandem mass spectroscopy. Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 20 protein markers of endothelial dysfunction. Baseline demographics did not differ between groups and parameters of response following IVF did not differ. Vitamins D₂ and D₃, and 1,25 Vitamin D₃ did not differ between groups. In UI, markers of endothelial activation/dysfunction were investigated; vascular cell adhesion molecule 1 (VCAM-1) decreased and this is associated with endothelial stress; vascular endothelial growth factor (VEGF) decreased and this may suggest impaired endometrial angiogenesis; while intercellular adhesion molecule 1 (ICAM-3) increased (p < 0.05) and is associated with increased immunological activity. A marker of vascular integrity, angiopoietin-1, increased while soluble angiopoietin-1 receptor (sTie-2) decreased (p < 0.05), suggesting increased vascular development. Endothelial markers of inflammation, coagulation, and endothelial progenitor cells were unchanged. Vitamin D and its metabolites show no relationship to UI, but endothelial activation/dysfunction and vascular integrity changes in VCAM-1, VEGF, sICAM-3, angiopoietin-1, and sTie-2 may contribute to UI, though the mechanisms through which they work require further evaluation; however, these protein changes have been associated with endometriosis, raising the suggestion that subclinical/undiagnosed endometriosis may have contributed to UI in these subjects. Full article

Stroke is still considered a predominant cause of morbidity and mortality, for which research on prevention and cure has been sought to prevent neuronal damage after a stroke incident. In this research, we evaluated the protective effects of virgin coconut oil (VCO) using behavioral, morphophysiological, and gene expression parameters using an ischemic stroke surgical rat model using Sprague Dawley (SD) rats. Eight-week-old SD rats were subjected to repeated oral administration (5 mL/kg/day) of either 1% Tween 80 or VCO. For behavioral and morphophysiological parameters, surgery was performed for each group, after which neurological scoring was performed at 4 h, 24 h, 48 h, 5 d, and 10 d. Further, hematological and brain morphology assessment was performed after euthanasia and necropsy of the animals. For gene expression studies, surgery was performed with animals sacrificed at different time points (baseline, before surgery, 4 h, 24 h, and 48 h after surgery) to collect the brain. Results of the study showed that there are differences in the neurological scores between the two treatments 24 h, 48 h, and 5 d after surgery. Brain morphology assessment also showed favorable results for VCO for infarct size, edema, and hypoxic neurons. Gene expression studies also showed positive results with an increase in the relative expression of angiogenin (Ang), angiopoietin (Angpt 1), Parkin, dynamin-related protein 1 (Drp 1), mitofusin 2 (Mfn 2), and mitochondrial rho (Miro) and decreased relative expression of caspase 3, receptor for advanced glycation end-product (Rage), and glyceraldehyde-3-phosphate dehydrogenase (Gapdh). In summary, the current study shows that VCO may have protective effects on the brain after stroke, which may be explained by the results of the gene expression studies. Full article

Neurological damage from traumatic spinal cord injury (SCI) results in a grade of disability ranging from mild to severe motor and sensory dysfunction. It occurs more frequently in men of productive age. Treatment essentially consists of anti-inflammatories and rehabilitation. Other treatments are only partially effective, and inadequate treatment and secondary conditions often cause premature mortality. The search for pharmacological approaches is a continuous effort. This study aimed to assess the effects of a natural compound on spinal cord injury (SCI) as an alternative damage prevention maneuver. We evaluated the protective effects of the flavanol (+)-epicatechin (EC) in a rat model of moderate trauma-induced SCI on protein markers of damage events. The results showed that EC induced significant protection against SCI. No changes were found in angiopoietin-1, beclin-1, myelin basic protein, glial fibrillary acidic protein, neurofilament heavy polypeptide, and neuronal nuclear antigen after the injury, suggesting that damage progression was impeded. The reduction in damage translates into better movement. The results suggest that (+)-epicatechin may be a suitable alternative for treating SCI. Full article

Background/Objectives: Major adverse cardiovascular events (MACE) are the primary cause of mortality among individuals with peripheral artery disease (PAD). Despite this, there is limited research on biomarkers that can predict MACE risk in this population. Proteins involved in angiogenesis are integral to both systemic circulation and the development of atherosclerosis, indicating their potential as prognostic markers. This study aimed to identify angiogenesis-related proteins associated with MACE risk in PAD patients. Methods: We conducted a prospective cohort study involving 250 patients diagnosed with PAD. At baseline, plasma levels of 17 angiogenesis-related proteins were measured. Participants were followed for two years, with the primary outcome being the incidence of MACE—a composite of stroke, myocardial infarction, or death. Protein concentrations were compared between those who experienced 2-year MACE and those who did not using the Mann–Whitney U test. Proteins showing significant differences were further analyzed using Cox proportional hazards modeling to assess their independent associations with MACE, adjusting for baseline demographic and clinical variables, including prior coronary and cerebrovascular disease. Kaplan–Meier survival analysis was also employed to compare MACE-free survival based on protein concentration levels. Results: The average age of participants was 69 years (SD 9), with 32% (n = 80) being female. Over the two-year follow-up, 48 patients (19.8%) experienced MACE. Among the proteins assessed, only hepatocyte growth factor (HGF) and angiopoietin-2 were significantly elevated in patients who developed MACE (HGF: 390.83 [SD 319.16] vs. 300.55 [SD 177.53] pg/mL, p < 0.001; angiopoietin-2: 23.67 [SD 17.60] vs. 19.36 [SD 12.06] pg/mL, p = 0.020). Multivariable Cox analysis confirmed that elevated levels of both HGF (adjusted HR 1.37; 95% CI 1.14–1.64; p = 0.001) and angiopoietin-2 (adjusted HR 1.27; 95% CI 1.04–1.55; p = 0.016) were independently associated with increased 2-year MACE risk. Kaplan–Meier curves demonstrated significantly reduced MACE-free survival in patients with higher levels of HGF and angiopoietin-2. Conclusions: HGF and angiopoietin-2 emerged as significant, independent predictors of 2-year MACE in patients with PAD. Measuring plasma levels of these proteins may enhance risk stratification, guiding referrals to appropriate cardiovascular specialists and informing the intensity of medical management. This biomarker-based precision medicine approach holds potential for improving cardiovascular outcomes in the PAD population. Full article

Angiopoietin-like proteins (ANGPTLs) represent a family of secreted glycoproteins that are extensively expressed in vivo and are integral to various pathophysiological processes, including glucose and lipid metabolism, stem cell proliferation, local inflammation, vascular permeability, and angiogenesis. Particularly interesting is ANGPTL4, which has been identified as a significant factor in the development and progression of diabetic retinopathy (DR), thus becoming a central focus of DR research. ANGPTLs modulate metabolic pathways, enhance vascular permeability, and facilitate pathological angiogenesis, in addition to causing intraocular inflammation. As promising molecular targets, ANGPTLs not only serve as biomarkers for predicting the onset and progression of DR but also present therapeutic potential through antibody-based interventions. This paper discusses the pathogenesis of DR and the potential applications of ANGPTLs in early diagnosis and targeted therapy. It provides references for advancing precision diagnosis and personalized treatment strategies through more profound ANGPTLs research in the future. Full article

Background: Cardiac involvement is a key prognostic factor in multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition that typically occurs 2–6 weeks after SARS-CoV-2 infection and is characterized by fever, systemic inflammation, and multiorgan involvement. Biomarkers may aid in early detection, severity assessment, and treatment stratification. Objective: To evaluate the diagnostic utility of established and emerging serum biomarkers in MIS-C, with an emphasis on cardiac dysfunction and disease severity. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to April 2025. Eligible studies included pediatric MIS-C cases with reported serum biomarkers. Meta-analyses were performed for NT-proBNP and troponin using random-effects models. Descriptive profiling was applied to emerging biomarkers. Subgroup comparisons were explored between severe and moderate MIS-C. Quality assessment followed the Newcastle–Ottawa Scale, and publication bias was assessed via funnel plots and Egger’s test. Results: A total of 67 studies were included, comprising >4000 pediatric MIS-C cases. NT-proBNP and troponin were consistently elevated (pooled means: 9697 pg/mL and 0.384 ng/mL, respectively), with a low risk of publication bias. Emerging biomarkers such as CXCL9, angiopoietin-2, and vitamin D revealed high inter-study variability but potential prognostic value. Subgroup analyses for selected studies (n = 5) suggested higher biomarker levels in severe MIS-C. Conclusions: NT-proBNP and troponin are robust indicators of cardiac injury in MIS-C. Emerging biomarkers show promise but require validation. Future studies should include copeptin and adopt standardized reporting to refine biomarker-guided management. Full article

Brain glioma is one of the most common malignant tumors of brain tissue. It is characterized by rich vascularization, which indicates the significant participation of angiogenesis in its growth and development. In its first stages, the disease is very often asymptomatic, and late diagnosis significantly limits possibilities of treatment. Tumor angiogenesis, i.e., the formation of new vessels, requires the presence of angiogenic compounds that will enable tumor progression by creating a path for the supply of nutrients. The proangiogenic compounds involved in the development of glioma include hypoxia-inducible factor 1α (HIF-1α), angiopoietin-2 (ANG-2), and interleukin-1β (IL-1β). The aim of this study was to analyze changes in the levels of these proteins in plasma samples of patients diagnosed with brain glioma in stages G1 to G4, and in a control group, using SPRi biosensors. The results obtained in plasma were compared with the concentrations obtained during the analysis of tissue homogenates from patients with glioma in stages G2 to G4. A statistically significant difference in plasma concentrations was obtained between the patient group and the control group. The concentrations of the markers in tissue homogenate samples were statistically higher than in blood plasma. There was no significant effect of gender, diet, smoking, or the patient’s general health condition (Karnofsky score) on the course of the disease. These factors do not directly increase the risk of developing brain glioma. Full article

Background: This study aimed to investigate the long-term effects of maternal exposure to fine particulate matter (PM_2.5) with or without vitamin D supplementation on the renal microvasculature in adult rat offspring. Methods: Pregnant Sprague–Dawley rats were exposed to normal saline, PM_2.5, and PM_2.5 with vitamin D for one month during nephrogenesis. Male offspring kidneys were taken for analyses on postnatal day 56. Results: Adult offspring rats exposed to maternal PM_2.5 exhibited lower body weights and greater glomerular and tubular injury scores compared to control rats. Semi-quantitative analysis revealed a significant reduction in glomerular and peritubular capillary endothelial cells, along with a decrease in the number of glomeruli in the PM_2.5 group. Maternal vitamin D supplementation reduced these changes. In offspring rats exposed to maternal PM_2.5, intrarenal expression of renin, angiotensin-converting enzyme (ACE), cytochrome P450 27B1, and vascular endothelial growth factor-A (VEGF-A) increased, while expression of the vitamin D receptor, Klotho, VEGF receptor 2, angiopoietin-1, and Tie-2 decreased. Maternal vitamin D supplementation restored VEGF receptor 2 and angiopoietin-1 activities and reduced ACE and VEGF-A protein expression in adult offspring kidneys. Conclusions: Early-life exposure to PM_2.5 may lead to long-term alterations in renal microvasculature and nephron loss. Maternal vitamin D supplementation during renal development can ameliorate PM_2.5-induced capillary rarefaction and nephron loss in the kidneys of adult offspring. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and impaired epithelial barrier function. Emerging evidence highlights the critical role of vascular remodeling and angiogenesis in IBD pathogenesis. This review explores the intricate relationship between blood vessels and the intestinal epithelial barrier, emphasizing how aberrant vascularization contributes to barrier dysfunction and disease progression. In IBD, excessive angiogenesis is driven by hypoxia, immune cell infiltration, and pro-inflammatory cytokines, further perpetuating inflammation and tissue damage. Key angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietins, and platelet-derived growth factor (PDGF), are upregulated in IBD, promoting pathological vessel formation. These newly formed vessels are often immature and hyperpermeable, exacerbating leukocyte recruitment and inflammatory responses. Given the pivotal role of angiogenesis in IBD, anti-angiogenic therapies have emerged as a potential therapeutic strategy. Preclinical and clinical studies targeting VEGF and other angiogenic pathways have shown promise in reducing inflammation and promoting mucosal healing. This review summarizes current knowledge on vascular–epithelial interactions in IBD, the mechanisms driving pathological angiogenesis, and the therapeutic potential of anti-angiogenic approaches, providing insights for future research and treatment development. Full article

This study utilized Mendelian randomization (MR) to investigate the impact of inflammatory proteins on knee osteoarthritis (KOA), measured using the ratio of protein levels (rQTLs). The primary objective was to identify potential intervention targets to mitigate KOA progression. Data from 2821 rQTLs, 91 inflammatory proteins, and KOA-related genetic variations were obtained through genome-wide association studies (GWAS). Bidirectional MR identified rQTLs with unidirectional causal relationships with KOA. Further analyses included false discovery rate (FDR) correction, colocalization, and mediation analysis. Two inflammatory proteins were found to be associated with KOA: T-cell surface glycoprotein CD5 [OR (95% CI) = 0.867 (0.760–0.990), P_IVW = 0.035] and C-X-C motif chemokine 9 [OR (95% CI) = 1.150 (1.001–1.320), P_IVW = 0.048]. Variations in their levels influenced rQTLs, producing differential effects on KOA. Specifically, rQTL-ANGPTL3/TFPI (human recombinant angiopoietin-like protein 3/Tissue factor pathway inhibitor) was identified as a mediator in the effect of T-cell surface glycoprotein CD5 levels on KOA. T-cell surface glycoprotein CD5 levels were negatively correlated with rQTL-ANGPTL3/TFPI (β1 = −0.084), while rQTL-ANGPTL3/TFPI was positively correlated with KOA (β2 = 0.159). These findings align with the total effect, where T-cell surface glycoprotein CD5 levels were negatively associated with KOA (β = −0.143). Thus, rQTL-ANGPTL3/TFPI may serve as a reliable mediator in the pathway through which T-cell surface glycoprotein CD5 levels affect KOA. This mediator may not only represent a potential therapeutic target but also serve as a biomarker for assessing KOA treatment efficacy, offering a novel direction for KOA diagnosis and management. Full article