SCUBE-1 in The Diagnosis and Follow-Up Of Subclinical Atherosclerosis in The Experimental Diabetes Mellitus and Obesity Model

BACKGROUND Obesity and diabetes mellitus (DM) is a metabolic disease that is a global problem, the most crucial complication of which is atherosclerotic cardiovascular disease resulting from endothelial dysfunction and accompanying platelet hyperactivity. The presence of the SCUBE-1 protein has been observed within vascular endothelial cells and platelets, both recognized for their pivotal involvement in the arterial thrombosis mechanism. The objective of this research is to examine the utility of serum SCUBE-1 levels in diagnosing and monitoring subclinical atherosclerosis in experimentally induced DM and obese rats. METHODS The study comprised a cohort of 28 male Sprague‒Dawleyrats, which encompassed the following groups: the obese group subjected to a high-fat diet (HFD), the TII-DM group administered HFD in combination with a single dose of streptozocin (STZ), the TI-DM group treated solely with STZ, and the control group. Serum SCUBE1 was analyzed using the enzyme-linked immunosorbent assay method, and caspase-3 (Cas-3), interleukin-6 (IL-6), interferon-gamma (INF-gamma) and superoxide dismutase (SOD) expression in the liver and pancreas of rats were evaluated using immunohistochemical methods. RESULTS Serum SCUBE1 levels were significantly higher in the obese and DM groups than in the control group, but there was no significant difference among the obese, TI-DM and TII-DM groups. The study identified a significant relationship between serum SCUBE1 level and hepatic CAS3, IL-6 and SOD expression and pancreatic SOD expression. CONCULISON SCUBE1 can be used as a promising novel marker for the diagnosis and monitoring of subclinical atherosclerosis in individuals with obesity, TI-DM, and TII-DM

[1]  S. Karahan,et al.  Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients? , 2023, Endocrine.

[2]  R. Ruze,et al.  Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments , 2023, Frontiers in Endocrinology.

[3]  C. Mertoğlu,et al.  Serum SCUBE-1 levels in patients with diabetic retinopathy , 2019, International Ophthalmology.

[4]  C. Vecchione,et al.  The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation , 2018, International journal of molecular sciences.

[5]  A. Şahin,et al.  The Diagnostic Value of Scube1 in Patients Presenting to the Emergency Department Due to Angina Pectoris , 2018, Kırıkkale Üniversitesi Tıp Fakültesi Dergisi.

[6]  O. Demir,et al.  Investigation of serum SCUBE-1 level in relation to microvascular complications in patients with type 2 diabetes mellitus , 2018 .

[7]  L. Bronze,et al.  SCUBE 1: A novel biomarker related to platelet activation and atherothrombosis. , 2018, Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology.

[8]  A. Alver,et al.  Investigation of the relationship between oxidative stress and SCUBE1 levels in high fat diet-induced obese rats , 2018, Turkish journal of medical sciences.

[9]  Frank B. Hu,et al.  Global aetiology and epidemiology of type 2 diabetes mellitus and its complications , 2018, Nature Reviews Endocrinology.

[10]  Joshua A. Salomon,et al.  Health Effects of Overweight and Obesity in 195 Countries over 25 Years. , 2017, The New England journal of medicine.

[11]  Dursun Akaslan,et al.  The role of SCUBE1 in the pathogenesis of no-reflow phenomenon presenting with ST segment elevation myocardial infarction , 2017, Anatolian journal of cardiology.

[12]  P. Vanhoutte,et al.  Macro‐ and microvascular endothelial dysfunction in diabetes , 2017, Journal of diabetes.

[13]  Gretchen A. Stevens,et al.  Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants , 2016, Lancet.

[14]  S. Şahin,et al.  The value of signal peptide-CUB-EGF domain-containing protein-1 (SCUBE1) in the diagnosis of pulmonary embolism: a preliminary study. , 2015, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[15]  Yunus Karaca,et al.  Diagnostic value of plasma signal peptide-Cub-Egf domain-containing protein-1 (SCUBE-1) in an experimental model of acute ischemic stroke. , 2015, The American journal of emergency medicine.

[16]  Ming-Huei Chen,et al.  Inhibition of the Plasma SCUBE1, a Novel Platelet Adhesive Protein, Protects Mice Against Thrombosis , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[17]  Yong Jiang,et al.  Scube regulates synovial angiogenesis-related signaling. , 2013, Medical hypotheses.

[18]  W. Ruf,et al.  Inflammation, obesity, and thrombosis. , 2012, Blood.

[19]  Sebastian M. Armasu,et al.  Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism , 2011, Journal of thrombosis and haemostasis : JTH.

[20]  R. DeFronzo Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009 , 2010, Diabetologia.

[21]  A. J. Gerrits,et al.  Platelet Tissue Factor Synthesis in Type 2 Diabetic Patients Is Resistant to Inhibition by Insulin , 2010, Diabetes.

[22]  P. Vanhoutte How We Learned to Say NO. , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[23]  E. Stępień,et al.  Hyperglycemia Is Associated With Enhanced Thrombin Formation, Platelet Activation, and Fibrin Clot Resistance to Lysis in Patients With Acute Coronary Syndrome , 2008, Diabetes Care.

[24]  Chien-Hsiun Chen,et al.  Plasma concentration of SCUBE1, a novel platelet protein, is elevated in patients with acute coronary syndrome and ischemic stroke. , 2008, Journal of the American College of Cardiology.

[25]  Chien-Jui Cheng,et al.  Domain and Functional Analysis of a Novel Platelet-Endothelial Cell Surface Protein, SCUBE1* , 2008, Journal of Biological Chemistry.

[26]  A. Vigé,et al.  C57BL/6J and A/J Mice Fed a High‐Fat Diet Delineate Components of Metabolic Syndrome , 2007, Obesity.

[27]  S. Marshall,et al.  Advanced glycation end products elicit externalization of phosphatidylserine in a subpopulation of platelets via 5-HT2A/2C receptors. , 2007, American journal of physiology. Cell physiology.

[28]  M. Tsai,et al.  Localization and characterization of a novel secreted protein SCUBE1 in human platelets. , 2006, Cardiovascular research.

[29]  R. Ramasamy,et al.  Protein Glycation: A Firm Link to Endothelial Cell Dysfunction , 2004, Circulation research.

[30]  R. DeFronzo,et al.  A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes. , 2003, Diabetes.

[31]  S. Colman,et al.  Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium* , 2002, The Journal of Biological Chemistry.

[32]  Zaverio M. Ruggeri,et al.  Platelets in atherothrombosis , 2002, Nature Medicine.

[33]  A. Pfeiffer,et al.  Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro , 2001, Diabetologia.

[34]  S. Grimmond,et al.  Cloning, mapping, and expression analysis of a gene encoding a novel mammalian EGF-related protein (SCUBE1). , 2000, Genomics.

[35]  L. Badimón,et al.  Platelet function in patients with familial hypertriglyceridemia: evidence that platelet reactivity is modulated by apolipoprotein E content of very-low-density lipoprotein particles. , 2000, Metabolism: clinical and experimental.

[36]  Microvascular Complications of Type 2 Diabetes Mellitus , 2020, Current Vascular Pharmacology.

[37]  M. Karabacak,et al.  The diagnostic role of signal peptide-C1r/C1s, Uegf, and Bmp1-epidermal growth factor domain-containing protein 1 in non-ST-elevation acute coronary syndrome. , 2015, The American journal of emergency medicine.

[38]  C. Homko,et al.  Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. , 2006, Diabetes.

[39]  Andreas Schober,et al.  Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E , 2003, Nature Medicine.