Are platelets the primary culprits in acute coronary syndrome? Some recent studies imply…
…that platelets are involved in both plaque formation and plaque rupture.
I leave today, July 16, 2007, for the American Society for Clinical Laboratory Science (www.ascls.org) and American Society for Clinical Chemistry (www.aacc.org) annual meeting in San Diego. Friday, I’m giving a 90-minute presentation entitled “The Role of Platelets in Cardiac Disease: Markers of Risk.” I’m less comfortable presenting principles and mechanisms than laboratory applications and clinical responses, but my study has turned up some new and exciting information. You may want to refer to Berndt MC, Karunakaran D, Gardiner EE, Andrews RK. Programmed autologous cleavage of platelet receptors. J Thromb Haemost 2007;5(Suppl. 1) 212-9.
It turns out that two key platelet adhesion molecules, GPIb/IX/V (the von Willebrand factor binding site) and GPVI (one of the collagen binding sites), play an important role in propagating atherosclerosis by binding monocytes. To add injury to insult, these receptors trigger platelet activation in areas of unstable atherosclerotic plaque, leading to clot formation and acute coronary syndrome.
Further, two enzymes, ADAM10 and ADAM17, members of the metalloproteinase family that includes the von Willebrand cleaving protease, ADAM13 (ADAMTS13), seem to regulate these receptors by cleaving them at the point where they enter the membrane, a process called ectodomain shedding.
This appears to be a fruitful area of cardiovascular disease research and molecular therapy. For example, platelet surface GPVI levels rise several hours before troponin, sometime before the actual cardiac event, making them an imminent emergency
department predictor. Further, several snake venoms mimic the “ADAMs family” (my name) enzymes, triggering a possible research path.
We may be performing more and more platelet marker laboratory tests as we pursue their relationship to cardiovascular disease. Geo