Clots, kinins and coronaries.
The dynamic regulation of intravascular thrombus formation is central to our understanding of both acute and chronic atherosclerotic events. The initiation, modification and resolution of thrombus associated with eroded or unstable coronary plaques is critically dependent on the efficacy of endogenous fibrinolysis, a process that is itself reliant upon the cellular activation and function of the surrounding endothelium and vascular wall. Bradykinin is a vasodilator peptide that stimulates the endothelium to release the pro-lytic factor, tissue-type plasminogen activator and is released at sites of intravascular thrombus formation including the luminal surface of ruptured or eroded atheromatous plaques. Recent studies have provided important and novel insights into the contribution of bradykinin to the regulation of endogenous fibrinolysis and intravascular thrombosis in the peripheral and coronary circulations in vivo in man. Moreover, the pro-fibrinolytic effects of bradykinin are markedly augmented in the presence of angiotensin-converting enzyme inhibition and may explain, at least in part, the established anti-ischaemic effects of angiotensin-converting enzyme inhibitors in patients with atherosclerosis. The development of novel agents that potentiate bradykinin and endogenous fibrinolysis, such as inhibitors of thrombin activatable fibrinolysis inhibitor, may provide future therapeutic strategies to treat and prevent cardiovascular disease.
Cruden
Nicholas L M
NL
Department of Cardiology, Royal Infirmary of Edinburgh, Little France, Edinburgh EH16 5SA, UK. nick cruden@ed.ac.uk
Newby
David E
DE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001920:Bradykinin / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D003326:Coronary Circulation; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin