The application of proteomics technology to thrombosis research: the identification of potential therapeutic targets in cardiovascular disease.
Thrombus formation underpins the development of cardiovascular diseases, including acute coronary syndromes and ischaemic stroke. A number of well-characterised cardiovascular risk factors which contribute to the development of the majority of cardiovascular events have been identified, including dyslipidaemia, hypertension and diabetes. Individuals with type 2 diabetes mellitus (T2DM) have a 3- to 5-fold increased risk for development of cardiovascular disease (CVD). They may have a cluster of haemostatic abnormalities, including elevated levels of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen, which contribute to acute thrombotic events. It is clear that additional unidentified risk factors contribute to the pathogenesis of cardiovascular events, and so the search for novel biomarkers and effectors, particularly in individuals with T2DM, remains a major challenge of cardiovascular medicine. Plasma and cellular proteins which contribute to thrombus formation have the potential to confer a pro-thrombotic state and represent a link between genotype, environment and disease phenotype. The comprehensive analysis of these proteins is now increasingly facilitated through the continued development of proteomic technologies which provide multifaceted approaches to the identification of novel biomarkers and/or effectors of thrombus formation and on which future anticoagulant and thrombolytic therapies may be based. This review provides an overview of current proteomic technologies. It focuses on the recent studies in which these technologies have been applied in the search for novel proteins that may confer increased risk of acute cardiovascular diseases and therefore that may influence disease progression and therapy.
Howes
Joanna-Marie
JM
Division of Cardiovascular & Diabetes Research, The LIGHT Laboratories, University of Leeds, LS2 9JT, UK.
Keen
Jeff N
JN
Findlay
John Bc
JB
Carter
Angela M
AM
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D035843:Biomedical Research / Q000379:methods*; D001777:Blood Coagulation / Q000187:drug effects; D018450:Disease Progression; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D040901:Proteomics; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
D000925:Anticoagulants; D015415:Biomarkers; D005343:Fibrinolytic Agents