Potential therapeutic targeting of platelet-mediated cellular interactions in atherosclerosis and inflammation.
Cellular interactions among platelets, leukocytes and endothelial cells are considered as a major cause of inflammation and atherosclerosis in many diseases. Via exposed surface receptors and released soluble substances, activated platelets play a crucial role in the initiation of inflammatory processes, resulting in endothelial injury and leading to formation of atherosclerotic plaque with possible thrombotic complications. Classic anti-platelet treatments (e.g. cyclooxygenase inhibitor or ADP-receptor antagonist) have favorable effects in patients with vascular diseases, but they also have several limitations such as increased bleeding risk or non-responsiveness. Thus, the need and opportunities for developing novel therapeutic inhibitors for platelet-mediated events are obvious. Animal and (pre)clinical human studies have suggested that some recently produced specific antagonists of P-selectin from α-granules, as well as its main ligand/receptor P-selectin Glycoprotein Ligand-1, the two major platelet chemokines CXCL4 and CCL5, as well as CD40L, may be considered potential new candidates in the treatment of atherogenesis and inflammation. In this review, we summarize the pathophysiological roles of these effectors in platelet activation and acute or chronic inflammation, and discuss the latest findings on promising antagonistic agents in basic and clinical studies in the prevention of platelet-mediated cellular interactions.
Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
B
B
Nagy
K
K
Miszti-Blasius
A
A
Kerenyi
K J
KJ
Clemetson
J
J
Kappelmayer
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors