-
Journal of Nuclear Cardiology :... Aug 2023
Topics: Humans; Antihypertensive Agents; Atherosclerosis; Hypertension
PubMed: 37138176
DOI: 10.1007/s12350-023-03272-w -
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 -
Cold Spring Harbor Perspectives in... Mar 2023Angiogenesis, the growth of new blood vessels, plays a critical role in tissue repair and regeneration, as well as in cancer. A paradigm shift is emerging in our... (Review)
Review
Angiogenesis, the growth of new blood vessels, plays a critical role in tissue repair and regeneration, as well as in cancer. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving mediators (SPMs), including resolvins. Angiogenesis and the resolution of inflammation are critical interdependent processes. Disrupted inflammation resolution can accelerate tumor growth, which is angiogenesis-dependent. SPMs, including resolvins and lipoxins, inhibit physiologic and pathological angiogenesis at nanogram concentrations. The failure of resolution of inflammation is an emerging hallmark of angiogenesis-dependent diseases including arthritis, psoriasis, diabetic retinopathy, age-related macular degeneration, inflammatory bowel disease, atherosclerosis, endometriosis, Alzheimer's disease, and cancer. Whereas therapeutic angiogenesis repairs tissue damage (e.g., limb ischemia), inhibition of pathological angiogenesis suppresses tumor growth and other non-neoplastic diseases such as retinopathies. Stimulation of resolution of inflammation via pro-resolving lipid mediators promotes the repair of tissue damage and wound healing, accelerates tissue regeneration, and inhibits cancer. Here we provide an overview of the mechanisms of cross talk between angiogenesis and inflammation resolution in chronic inflammation-driven diseases. Stimulating the resolution of inflammation via pro-resolving lipid mediators has emerged as a promising new field to treat angiogenic diseases.
Topics: Humans; Inflammation; Atherosclerosis; Ischemia; Lipids; Neovascularization, Pathologic; Inflammation Mediators
PubMed: 35817542
DOI: 10.1101/cshperspect.a041172 -
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 -
Advances in Protein Chemistry and... 2020The term atherosclerosis refers to the condition of deposition of lipids and other substances in and on the artery walls, called as plaque that restricts the normal... (Review)
Review
The term atherosclerosis refers to the condition of deposition of lipids and other substances in and on the artery walls, called as plaque that restricts the normal blood flow. The plaque may be stable or unstable in nature. Unstable plaque can burst and trigger clot formation adding further adversities. The process of plaque formation involves various stages including fatty streak, intermediate or fibro-fatty lesion and advanced lesion. The cells participating in the formation of atherosclerotic plaque include endothelial cells, vascular smooth muscle cells (VSMC), monocytes, monocytes derived macrophages, macrophages and dendritic cells and regulatory T cells (T). The role of a variety of cytokines and chemokines have been studied which either help in progression of atherosclerotic plaque or vice versa. The cytokines involved in atherosclerotic plaque formation include IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IL-18, IL-20, IL-25, IL-27, IL-33, IL-37, TNF-α, TGF-β and IFN-γ; whereas amongst the chemokines (family of small cytokines) are CCL2, CCL3, CXCL4, CCL5, CXCL1, CX3CL1, CCL17, CXCL8, CXCL10, CCL20, CCL19 and CCL21 and macrophage migration-inhibitory factor. These are involved in the atherosclerosis advancements, whereas the chemokine CXCL12 is play atheroprotective roles. Apart this, contradictory functions have been documented for few other chemokines such as CXCL16. Since the cytokines and chemokines are amongst the key molecules involved in orchestrating the atherosclerosis advancements, targeting them might be an effective strategy to encumber the atherosclerotic progression. Blockage of cytokines and chemokines via the means of broad-spectrum inhibitors, neutralizing antibodies, usage of decoy receptors or RNA interference have been proved to be useful intervention against atherosclerosis.
Topics: Animals; Atherosclerosis; Cytokines; Humans
PubMed: 32085889
DOI: 10.1016/bs.apcsb.2019.11.002 -
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 -
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 -
Expert Opinion on Therapeutic Targets Aug 2020
Topics: Animals; Atherosclerosis; Disease Progression; Epigenesis, Genetic; Humans; Molecular Targeted Therapy; Plaque, Atherosclerotic
PubMed: 32354276
DOI: 10.1080/14728222.2020.1764535