title: Tribbles 3: A potential player in diabetic aortic remodelling.
abstract: Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ti
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China Department of Cardiology, Tianjin Chest Hospital, Tianjin, P.R. China.
authors.forename: Guo-lu
authors.initials: GL
authors.lastname: Xie
authors.affiliation: Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, P.R. China.
authors.forename: Zhi-hao
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China.
authors.forename: Wen-yuan
authors.initials: WY
authors.lastname: Ding
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, P.R. China zhangweisdu@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D003187:Compliance; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D017553:Phosphorus Compounds; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D066253:Vascular Remodeling / Q000235:genetics*
chemical_list: D003094:Collagen; D048670:MAP Kinase Kinase 4; D019869:Phosphatidylinositol 3-Kinases; D017553:Phosphorus Compounds; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C502443:Trib3 protein, rat; C013196:phosphoryl chloride
keywords: Tribbles 3; ageing; diabetes; gene silencing; insulin resistance; vascular remodelling