title: Platelet Hyperreactivity in Diabetes: Focus on GPVI Signaling-Are Useful Drugs Already Available?
abstract: Adults with diabetes are 2-4 times more likely to suffer from heart disease or ischemic stroke than adults without diabetes, yet standard antiplatelet therapy, which is the cornerstone for primary and secondary prevention of cardiovascular disease, fails in many patients with diabetes. Three independent but often interrelated variables that contribute to platelet hyperreactivity-high blood glucose, oxidative stress, and elevated vascular shear forces-coexist in patients with diabetes, creating a perilous concurrence of risk factors for cardiovascular events. Recent research has focused attention on the platelet-specific collagen receptor glycoprotein VI (GPVI) as a potential antithrombotic target. Signaling events downstream of GPVI are influenced by hyperglycemia, oxidative stress, and shear stress. Importantly, drugs targeting these GPVI signaling pathways are already in existence. The potential to repurpose existing drugs is a high-gain strategy for yielding new antiplatelet agents and could have particular benefit in individuals with diabetes.
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Australia jane.arthur@monash.edu.
authors.forename: Jane F
authors.identifier: http://orcid.org/0000-0001-9176-2243
authors.initials: JF
authors.lastname: Arthur
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: Jandeleit-Dahm
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Andrews
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000378:metabolism / Q000517:prevention & control*; D003920:Diabetes Mellitus / Q000097:blood* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI