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Stroke and Vascular Neurology Apr 2024Atherosclerosis (AS) and tumours are the leading causes of death worldwide and share common risk factors, detection methods and molecular markers. Therefore, searching...
BACKGROUND
Atherosclerosis (AS) and tumours are the leading causes of death worldwide and share common risk factors, detection methods and molecular markers. Therefore, searching for serum markers shared by AS and tumours is beneficial to the early diagnosis of patients.
METHODS
The sera of 23 patients with AS-related transient ischaemic attack were screened by serological identification of antigens through recombinant cDNA expression cloning (SEREX), and cDNA clones were identified. Pathway function enrichment analysis was performed on cDNA clones to identify their biological pathways and determine whether they were related to AS or tumours. Subsequently, gene-gene and protein-protein interactions were performed and AS-associated markers would be discovered. The expression of AS biomarkers in human normal organs and pan-cancer tumour tissues were explored. Then, immune infiltration level and tumour mutation burden of various immune cells were evaluated. Survival curves analysis could show the expression of AS markers in pan-cancer.
RESULTS
AS-related sera were screened by SEREX, and 83 cDNA clones with high homology were obtained. Through functional enrichment analysis, it was found that their functions were closely related to AS and tumour functions. After multiple biological information interaction screening and the external cohort validating, poly(A) binding protein cytoplasmic 1 (PABPC1) was found to be a potential AS biomarker. To assess whether PABPC1 was related to pan-cancer, its expression in different tumour pathological stages and ages was screened. Since AS-associated proteins were closely related to cancer immune infiltration, we investigated and found that PABPC1 had the same role in pan-cancer. Finally, analysis of Kaplan-Meier survival curves revealed that high PABPC1 expression in pan-cancer was associated with high risk of death.
CONCLUSIONS
Through the findings of SEREX and bioinformatics pan-cancer analysis, we concluded that PABPC1 might serve as a potential biomarker for the prediction and diagnosis of AS and pan-cancer.
Topics: Humans; Neoplasms; Male; Predictive Value of Tests; Middle Aged; Female; Atherosclerosis; Poly(A)-Binding Protein I; Biomarkers, Tumor; Protein Interaction Maps; Aged; Prognosis; Risk Assessment; Gene Regulatory Networks
PubMed: 37311641
DOI: 10.1136/svn-2022-002246 -
Journal of Nanobiotechnology May 2023PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin...
PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE mice.
Topics: Mice; Animals; Proprotein Convertase 9; Liposomes; Atherosclerosis
PubMed: 37208681
DOI: 10.1186/s12951-023-01904-4 -
Nutrients Aug 2020Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality worldwide [...].
Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality worldwide [...].
Topics: Atherosclerosis; Cholesterol; Diabetes Mellitus, Type 2; Diet, Mediterranean; Humans; Inflammation; Life Style; Nutritional Physiological Phenomena; Obesity
PubMed: 32823869
DOI: 10.3390/nu12082444 -
Circulation Sep 2021The necrotic core partly formed by ineffective efferocytosis increases the risk of an atherosclerotic plaque rupture. Microribonucleic acids contribute to necrotic core...
BACKGROUND
The necrotic core partly formed by ineffective efferocytosis increases the risk of an atherosclerotic plaque rupture. Microribonucleic acids contribute to necrotic core formation by regulating efferocytosis and macrophage apoptosis. Atherosclerotic plaque rupture occurs at increased frequency in the early morning, indicating diurnal changes in plaque vulnerability. Although circadian rhythms play a role in atherosclerosis, the molecular clock output pathways that control plaque composition and rupture susceptibility are unclear.
METHODS
Circadian gene expression, necrotic core size, apoptosis, and efferocytosis in aortic lesions were investigated at different times of the day in mice and mice after consumption of a high-fat diet for 12 weeks. Genome-wide gene expression and lesion formation were analyzed in bone marrow-transplanted mice. Diurnal changes in apoptosis and clock gene expression were determined in human atherosclerotic lesions.
RESULTS
The expression of molecular clock genes, lesional apoptosis, and necrotic core size were diurnally regulated in mice. Efferocytosis did not match the diurnal increase in apoptosis at the beginning of the active phase. However, in parallel with apoptosis, expression levels of oscillating strands decreased in the mouse atherosclerotic aorta. knockout abolished circadian regulation of apoptosis and reduced necrotic core size but did not affect core clock gene expression. Further, knockout upregulated expression of proapoptotic Xaf1 (XIAP-associated factor 1) in the atherosclerotic aorta, which abolished circadian expression of Xaf1. The antiapoptotic effect of was mediated by noncanonical targeting of through both strands. knockout in bone marrow cells also reduced atherosclerosis and necrotic core size. Circadian regulation of clock gene expression was confirmed in human atherosclerotic lesions. Apoptosis oscillated diurnally in phase with expression, demonstrating an early morning peak antiphase to that of the strands.
CONCLUSIONS
Our findings suggest that the molecular clock in atherosclerotic lesions induces a diurnal rhythm of apoptosis regulated by circadian expression in macrophages that is not matched by efferocytosis, thus increasing the size of the necrotic core.
Topics: Animals; Apoptosis; Atherosclerosis; Disease Models, Animal; Humans; Mice; Mice, Inbred C57BL; MicroRNAs
PubMed: 34233454
DOI: 10.1161/CIRCULATIONAHA.120.051614 -
Trends in Molecular Medicine Dec 2023Multiomics studies offer accurate preventive and therapeutic strategies for atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. By using... (Review)
Review
Multiomics studies offer accurate preventive and therapeutic strategies for atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. By using artificial intelligence (AI) and machine learning (ML) approaches, it is possible to integrate multiple 'omics and clinical data sets into tools that can be utilized for the development of personalized diagnostic and therapeutic approaches. However, currently multiple challenges in data quality, integration, and privacy still need to be addressed. In this opinion, we emphasize that joined efforts, exemplified by the AtheroNET COST Action, have a pivotal role in overcoming the challenges to advance multiomics approaches in ASCVD research, with the aim to foster more precise and effective patient care.
Topics: Humans; Artificial Intelligence; Cardiovascular Diseases; Multiomics; Atherosclerosis; Machine Learning
PubMed: 37806854
DOI: 10.1016/j.molmed.2023.09.004 -
Current Pharmaceutical Design 2017Over the past two decades, the viewpoint of atherosclerosis has been replaced gradually by a lipiddriven, chronic, low-grade inflammatory disease of the arterial wall.... (Review)
Review
Over the past two decades, the viewpoint of atherosclerosis has been replaced gradually by a lipiddriven, chronic, low-grade inflammatory disease of the arterial wall. Current treatment of atherosclerosis is focused on limiting its risk factors, such as hyperlipidemia or hypertension. However, treatment targeting the inflammatory nature of atherosclerosis is still very limited and deserves further attention to fight atherosclerosis successfully. Here, we review the current development of inflammation and atherosclerosis to discuss novel insights and potential targets in atherosclerosis, and to address drug discovery based on anti-inflammatory strategy in atherosclerotic disease.
Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; Drug Discovery; Humans; Inflammation
PubMed: 28034355
DOI: 10.2174/1381612822666161230142931 -
International Journal of Molecular... Apr 2015Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is... (Review)
Review
Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall;
Topics: Atherosclerosis; Biomechanical Phenomena; Contrast Media; Diagnostic Imaging; Humans; Risk Assessment; Ultrasonography
PubMed: 25938969
DOI: 10.3390/ijms16059749 -
Acta Pharmacologica Sinica Feb 2016Although various types of drugs and therapies are available to treat atherosclerosis, it remains a major cause of mortality throughout the world. Macrophages are the... (Review)
Review
Although various types of drugs and therapies are available to treat atherosclerosis, it remains a major cause of mortality throughout the world. Macrophages are the major source of foam cells, which are hallmarks of atherosclerotic lesions. Consequently, the roles of macrophages in the pathophysiology of atherosclerosis are increasingly investigated. Autophagy is a self-protecting cellular catabolic pathway. Since its discovery, autophagy has been found to be associated with a variety of diseases, including cardiovascular diseases, malignant tumors, neurodegenerative diseases, and immune system disorders. Accumulating evidence demonstrates that autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis and cholesterol efflux. These facts suggest the induction of autophagy may be exploited as a potential strategy for the treatment of atherosclerosis. In this review we mainly discuss the relationship between macrophage autophagy and atherosclerosis and the molecular mechanisms, as well as the recent advances in targeting the process of autophagy to treat atherosclerosis.
Topics: Animals; Atherosclerosis; Autophagy; Cholesterol; Drug Discovery; Humans; Inflammation; Macrophages; Molecular Targeted Therapy; Signal Transduction
PubMed: 26750103
DOI: 10.1038/aps.2015.87 -
Redox Biology Apr 2024Inflammatory macrophages are key drivers of atherosclerosis that can induce rupture-prone vulnerable plaques. Skewing the plaque macrophage population towards a more...
Inflammatory macrophages are key drivers of atherosclerosis that can induce rupture-prone vulnerable plaques. Skewing the plaque macrophage population towards a more protective phenotype and reducing the occurrence of clinical events is thought to be a promising method of treating atherosclerotic patients. In the current study, we investigate the immunomodulatory properties of itaconate, an immunometabolite derived from the TCA cycle intermediate cis-aconitate and synthesised by the enzyme Aconitate Decarboxylase 1 (ACOD1, also known as IRG1), in the context of atherosclerosis. Ldlr atherogenic mice transplanted with Acod1 bone marrow displayed a more stable plaque phenotype with smaller necrotic cores and showed increased recruitment of monocytes to the vessel intima. Macrophages from Acod1 mice contained more lipids whilst also displaying reduced induction of apoptosis. Using multi-omics approaches, we identify a metabolic shift towards purine metabolism, in addition to an altered glycolytic flux towards production of glycerol for triglyceride synthesis. Overall, our data highlight the potential of therapeutically blocking ACOD1 with the aim of stabilizing atherosclerotic plaques.
Topics: Humans; Animals; Mice; Plaque, Atherosclerotic; Atherosclerosis; Succinates; Macrophages
PubMed: 38309122
DOI: 10.1016/j.redox.2024.103054 -
Journal of Atherosclerosis and... Feb 2018Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease... (Review)
Review
Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease cathepsins play a pivotal role in extracellular matrix (ECM) remodeling and have been implicated in the development and progression of atherosclerosis-based cardiovascular diseases. An imbalance in expression between cathepsins (such as cathepsins S, K, L, C) and their inhibitor cystatin C may favor proteolysis of ECM in the pathogenesis of cardiovascular disease such as atherosclerosis, aneurysm formation, restenosis, and neovascularization. New insights into cathepsin functions have been made possible by the generation of knockout mice and by the application of specific inhibitors. Inflammatory cytokines regulate the expression and activities of cathepsins in cultured vascular cells and macrophages. In addition, evaluations of the possibility of cathepsins as a diagnostic tool revealed that the circulating levels of cathepsin S, K, and L, and their endogenous inhibitor cystatin C could be promising biomarkers in the diagnosis of coronary artery disease, aneurysm, adiposity, peripheral arterial disease, and coronary artery calcification. In this review, we summarize the available information regarding the mechanistic contributions of cathepsins to ASCVD.
Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Cathepsins; Humans
PubMed: 28978867
DOI: 10.5551/jat.RV17016