High Proteoglycan Decorin Levels Are Associated With Acute Coronary Syndrome and Provoke an Imbalanced Inflammatory Response.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhuang L
PROVIDER: S-EPMC8490816 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Proteoglycans are emerging as critical regulators of intracellular catabolism. This rise in prominence has transformed our basic understanding and alerted us to the existence of non-canonical pathways, independent of nutrient deprivation, that potently control the autophagy downstream of a cell surface receptor. As a member of the small leucine-rich proteoglycan gene family, decorin has single-handedly pioneered the connection between extracellular matrix signaling and autophagy regulation. Soluble decorin evokes protracted endothelial cell autophagy via Peg3 and breast carcinoma cell mitophagy via mitostatin by interacting with VEGFR2 or the MET receptor tyrosine kinase, respectively. In this paper, we give a mechanistic perspective of the vital factors underlying the nutrient-independent, SLRP-dependent programs utilized for autophagic and/or mitophagic progression in breast cancer. Future protein therapies based on decorin (or fellow proteoglycan members) will represent a quantum leap forward in transforming autophagic progression into a powerful tool to control intracellular cell catabolism from the outside.
| S-EPMC8834502 | biostudies-literature
Project description:BackgroundThe systemic inflammatory response index (SIRI) is a novel inflammatory biomarker in many diseases.ObjectivesThe aim of this study was to examine the association between SIRI and adverse events in patients with the acute coronary syndrome (ACS) undergoing percutaneous coronary intervention.MethodsA total of 1724 patients with ACS enrolled from June 2016 to November 2017 at a single centre were included in this study, and SIRI was calculated for each patient. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall death, non-fatal myocardial infarction, non-fatal stroke, and unplanned repeat revascularization.ResultsDuring a median follow-up of 927 days, 355 patients had MACE. Multivariate Cox analysis showed that SIRI was significantly associated with MACE (hazard ratio: 1.127, 95% confidence interval: 1.034-1.229 p = .007). The results were consistent in multiple sensitivity analyses. The addition of SIRI had an incremental effect on the predictive ability of the Global Registry of Acute Coronary Events risk score for MACE (integrated discrimination improvement: 0.007, p = .040; net reclassification improvement: 0.175, p = .020; likelihood ratio test: p < .001). The restricted cubic spline showed a monotonic increase with a greater SIRI value for MACE (p < .001).ConclusionSIRI was an independent risk factor for MACE and provided incremental prognostic information in patients with ACS undergoing percutaneous coronary intervention. KEY MESSAGESThe SIRI is a strong and independent risk factor for adverse outcomes in patients with ACS undergoing percutaneous coronary intervention.Higher SIRI is associated with a more severe disease status.The SIRI could increase the prognostic value of the GRACE risk score.
| S-EPMC9225721 | biostudies-literature
Project description:Background:Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance. Methods:A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results:The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively). Conclusions:The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.
| S-EPMC6006811 | biostudies-literature
Project description:The paramedics brought a 60-year-old man to the emergency department after a sudden onset of shortness of breath with a subsequent drop in the Glasgow Coma Scale (GCS). On arrival the patient looked peri-arrest. His O2 saturations were 84% on 15?L of oxygen. He had gasping breathing with a completely silent chest and the GCS was 6/15 (E=1, V=1, M=4). The blood gas revealed type-2 respiratory failure. The chest X-ray was unremarkable and ECG was not indicative for cardiac catheterisation lab activation. Bedside shock scan was done which showed global hypokinesia of the left ventricle. In spite of unconvincing ECG and chest X-ray, an acute cardiac event was diagnosed in view of an abnormal bedside echo. The patient was transferred to the cardiac catheterisation lab for urgent percutaneous coronary intervention which revealed critical stenosis of the left main stem coronary artery, which was successfully stented. The patient had a good recovery from the life-threatening event.
| S-EPMC4054466 | biostudies-other
Project description:AimsBiomarkers are essential in the early detection of acute coronary syndromes (ACS). Serum extracellular vesicles are small vesicles in the plasma containing protein and RNA and have been shown to be involved in ACS-related processes like apoptosis and coagulation. Therefore, we hypothesized that serum extracellular vesicle protein levels are associated with ACS.Methods and resultsThree serum extracellular vesicle proteins potentially associated with ACS were identified with differential Q-proteomics and were evaluated in 471 frozen serum samples of ACS-suspected patients presenting to the emergency department (30% of whom had an ACS). Protein levels were measured after vesicle isolation using ExoQuick. Mean serum extracellular vesicle concentration of the different proteins was compared between ACS and non-ACS patients. Selected proteins were tested in a univariate logistic regression model, as well as in a multivariate model to adjust for cardiovascular risk factors. A separate analysis was performed in men and women. In the multivariate logistic regression analysis, polygenic immunoglobulin receptor, (pIgR; OR 1.630, p=0.026), cystatin C (OR 1.641, p=0.021), and complement factor C5a (C5a, OR 1.495, p=0.025) were significantly associated with ACS, while total vesicle protein concentration was borderline significant. The association of the individual proteins with ACS was markedly stronger in men.ConclusionsThese data show that serum extracellular vesicle pIgR, cystatin C, and C5a concentrations are independently associated with ACS and that there are pronounced gender differences. These observations should be validated in a large, prospective study to assess the potential role of vesicle content in the evaluation of patients suspected of having an ACS.
| S-EPMC3760575 | biostudies-literature
Project description:Decorin (DCN) is a proteoglycan belonging to the small leucine-rich proteoglycan family. It is composed of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate. DCN is a structural component of connective tissues that can bind to type I collagen. It plays a role in the assembly of the extracellular matrix (ECM), and it is related to fibrillogenesis. It can interact with fibronectin, thrombospondin, complement component C1, transforming growth factor (TGF), and epidermal growth factor receptor. Normal DCN expression regulates a wide range of cellular processes, including proliferation, migration, apoptosis, and autophagy, through interactions with various molecules. However, its aberrant expression is associated with oocyte maturation, oocyte quality, and poor extravillous trophoblast invasion of the uterus, which underlies the occurrence of preeclampsia and intrauterine growth restriction. Spatiotemporal hormonal control of successful pregnancy should regulate the concentration and activity of specific proteins such as proteoglycan participating in the ECM remodeling of trophoblastic and uterine cells in fetal membranes and uterus. At the human feto-maternal interface, TGF-β and DCN play crucial roles in the regulation of trophoblast invasion of the uterus. This review summarizes the role of the proteoglycan DCN as an important and multifunctional molecule in the physiological regulation of oocyte maturation and trophoblast migration. This review also shows that recombinant DCN proteins might be useful for substantiating diverse functions in both animal and in vitro models of oogenesis and implantation.
| S-EPMC8651757 | biostudies-literature
Project description:The inhibition of platelet function by antiplatelet therapy determines the improvement of the survival of patients with clinically evident cardiovascular disease. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, major adverse cardiovascular events including stent thrombosis occur in patients taking clopidogrel and aspirin. A growing body of evidence demonstrates that high post-treatment platelet reactivity on antiplatelet treatment is associated with increased risk of adverse clinical events. Clopidogrel requires conversion to active metabolite by cytochrome P450 isoenzymes. The active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to P2Y(12) receptors. Recently, the loss-of-function CYP2C19*2 allele has been associated with decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, the CYP2C19*2 polymorphism is a strong predictor of adverse cardiovascular events and particularly of stent thrombosis. Prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients, CYP2C19*2 genotypes, platelet phenotype, drug-drug interaction, as well as traditional and procedural risk factors, are now urgently needed for the identification of therapeutic strategies providing the best benefit for the single subject.
| S-EPMC3513207 | biostudies-literature
Project description:Studies have implicated the extracellular matrix (ECM) of adipose tissue in insulin resistance. The proteoglycan decorin, a component of ECM, has been associated with glucose tolerance, but possible causal effects on metabolism remain to be explored. We here sought to determine metabolic consequences of loss of decorin in mice (DcnKO). DcnKO mice were fed a low-fat (LF) or high-fat (HF) diet for 10 weeks and body weight and food intake was recorded. An intraperitoneal glucose tolerance test was performed after eight weeks. Blood samples and adipose, liver and muscle tissues were collected at sacrifice. Global gene expression was measured in adipose tissue, and expression of decorin was also analyzed in human adipose samples. DcnKO mice showed increased feed efficiency during overfeeding and impaired glucose tolerance. Adipose leptin mRNA and circulating leptin levels were elevated in DcnKO mice, along with a downregulation of genes involved in ECM organization and triglyceride biosynthesis, and an upregulation of adipose genes involved in complement and coagulation cascades. Consistent with a protective metabolic role for decorin, in obese patients we found increased adipose decorin expression after profound fat loss, particularly in the stromal vascular fraction. Loss of decorin in mice caused impaired glucose tolerance in association with increased feed efficiency and altered gene expression in adipose tissue. Our data provide evidence that decorin is an important factor for maintaining glucose tolerance.
| S-EPMC6420637 | biostudies-literature
Project description:BackgroundThe discovery of novel biomarkers that improve current cardiovascular risk prediction models of acute coronary syndrome (ACS) is needed for the identification of very high-risk patients and therapeutic decision-making. Autophagy is a highly conserved catabolic mechanism for intracellular degradation of cellular components through lysosomes. The autophagy process helps maintain cardiac homeostasis and dysregulated autophagy has been described in cardiovascular conditions. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) is a key regulator of autophagy with a potential role in cardiac stress.ObjectivesThe aims of the present study were to assess whether changes in circulating Rubicon levels are associated with ACS and to evaluate the added value of Rubicon to a clinical predictive risk model.Methods and resultsThe study population included ACS patients (n = 100) and control subjects (n = 99) at high to very high cardiovascular risk but without known coronary event. Plasma Rubicon levels were measured in the whole study population by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses established that Rubicon levels were inversely associated with ACS. A receiver operating characteristic curve analysis demonstrated that the addition of Rubicon improved the predictive performance of the model with an increased area under the curve from 0.868 to 0.896 (p = 0.038).ConclusionsPlasma levels of the autophagy regulator Rubicon are associated with ACS and provide added value to classical risk markers for ACS.
| S-EPMC10796531 | biostudies-literature
Project description:A healthy 66-year-old female presented to the emergency department with acute chest pain, T-wave inversion in the anterior leads, and elevated troponin-I. Coronary angiography showed a stenosis in the midportion of the left anterior descending coronary artery (LAD), which did not wrap the left ventricle (LV) apex. LV angiography demonstrated a large LV apical akinetic systolic ballooning with a 45% ejection fraction. Fractional flow reserve (FFR) of LAD lesion was 0.71. Percutaneous intervention was performed. At six months, transthoracic echocardiography was normal. Fifteen months later, the patient presented with chest pain and a small rise in troponin-I. Coronary angiogram was unchanged. Repeat FFR in distal LAD was 0.86 and left ventriculography was normal. Diagnostic criteria for Takotsubo cardiomyopathy (TTC) require the absence of obstructive coronary artery disease. In the present case, TTC was highly suspected on the basis of typical LV apex ballooning. However, significant ischemia in the same territory was demonstrated by positive FFR, which could not be falsely positive in this context. Current TTC diagnostic criteria increase specificity for diagnosing TTC. This case reminds us that it is at the price of reduced sensitivity, since there is no reason to believe that coronary lesions may protect from TTC.
| S-EPMC7060413 | biostudies-literature