title: Kinase-SUMO networks in diabetes-mediated cardiovascular disease.
abstract: Type II diabetes mellitus (DM) is a common comorbidity in patients with cardiovascular disease (CVD). Epidemiological studies including the Framingham, UKPDS, and MRFIT studies have shown diabetes to be an independent risk factor for cardiovascular disease associated with increased incidence of morbidity and mortality. However, major randomized controlled clinical trials including ADVANCE, VAD, and ACCORD have failed to demonstrate a significant reduction in CVD complications from longstanding DM with strict glycemic control. This suggests that despite the strong clinical correlation between DM and CVD, the precise mechanisms of DM-mediated CVD pathogenesis remain unclear. Signal transduction investigations have shed some light on this question with numerous studies demonstrating the role of kinase pathways in facilitating DM and CVD pathology. Abnormalities in endothelial, vascular smooth muscle, and myocardial function from the pathological insults of hyperglycemia and oxidative stress in diabetes are thought to accelerate the development of cardiovascular disease. Extensive interplay between kinase pathways that regulate the complex pathology of DM-mediated CVD is heavily regulated by a number of post-translational modifications (PTMs). In this review, we focus on the role of a dynamic PTM known as SUMOylation and its role in regulating these kinase networks to provide a mechanistic link between DM and CVD.
authors.affiliation: Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Chang
authors.affiliation: Department of Cardiology - Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jabe@mdanderson.org.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Abe
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008955:Models, Cardiovascular; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D014657:Vasculitis / Q000150:complications / Q000503:physiopathology
chemical_list: D011494:Protein Kinases
keywords: SUMOylation; Type II diabetes mellitus; cardiovascular disease