Abstract 421: Biomarkers of Atherosclerotic Plaque Instability in Carotid Artery Stenosis
Objective: Atherosclerotic plaque instability has been linked to cardiovascular events. We hypothesized that novel serum and intraplaque markers of plaque instability could be identified through analysis of serum and atherosclerotic plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarterectomy (CEA).
Methods: Under an IRB approved protocol, 6 symptomatic patients (5 transient ischemic attack, 1 amaurosis fugax) and their age- and gender-matched controls were analyzed for intraplaque markers of plaque instability. 8 symptomatic patients and their age- and gender-matched controls were analyzed for serum activity of proteolytic enzymes MMP-2 and MMP-9. Plaques were removed intraoperatively, placed in RNAlater and processed immediately after CEA. Blood samples were drawn prior to incision to determine serum activity of MMP-2 and MMP-9 using gelatin zymography. Intraplaque expression of MMP-2, MMP-9, proteolytic enzymes (uPA, tPA and PAI-1) and inflammatory markers (TF, TSP-1, and TNF-α) were evaluated by Western blot analysis.
Results: The activity of proteolytic enzymes MMP-2 and MMP-9 detected in serum was significantly higher in symptomatic patients when compared to asymptomatic controls, with a 1.5- and 2.2-fold increase, respectively (P<0.05, n=8). The activity of MMP-2 and MMP-9 detected in plaque was also elevated in the symptomatic group, with a 9.04 and 15.3-fold increase, respectively. Intraplaque expression of uPA (9.6-fold increase) and PAI-1 (28% decrease) was found in symptomatic patients. The expression of inflammatory markers TF and TSP-1 was elevated in symptomatic patients (2.7- and 4.2-fold, respectively) (All P<0.05, n=6). There was not a statistically significant difference in levels of tPA and TNF-α (P=0.075 and 0.345, respectively).
Conclusion: Levels of matrix metalloproteinases, proteolytic enzymes and inflammatory markers found in serum and plaque samples of symptomatic and asymptomatic patients may be different. Testing for biomarkers may help diagnose atherosclerotic plaque instability and identify patients at high risk for cerebrovascular events.
- © 2012 by American Heart Association, Inc.