BACKGROUND: TSP-1 is a vasoconstrictive protein, which is released from both
endothelium and cardiomyocytes during ischemia and promotes platelet aggregation
and adhesion to subendothelial layers in atherosclerotic lesions. During
myocardial ischemia and reperfusion, TSP-1 disturbs local microcirculation by
disrupting both NO-signaling as well as VEGF-pathways by activation of CD47 and
CD36. Furthermore, activation of TGF-ß might induce excessive fibrosis after
infarction. It was assumed that TSP-1 is washed out after successful coronary
reperfusion. In this study, we examined circulating TSP-1 post emergency PCI as a
risk factor for major adverse cardiac events after STEMI with and without
ventricular fibrillation.
METHODS: TSP-1 levels in platelet poor plasma were measured in 54 patients after
ST-elevation myocardial infarction. Major adverse cardiac events were monitored
for 426 days.
RESULTS: Patients with decreased TSP levels after coronary stenting showed a
significantly higher risk for MACE than patient with higher TSP levels
(TSP-1[d0]: n = 46, no MACE = 16.38 ± 1.98 ug/mL vs. MACE 7.11 ± 1.54 ug/mL; p =
0.003). Kaplan-Meyer-analysis for MACE showed a better outcome above 10 ug/mL (p
= 0.02). For MACE later than 3 months post-STEMI, the corresponding
Kaplan-Meier-analysis yielded a p-value of 0.01. The number needed to diagnose
for late MACE was 2.158.
CONCLUSION: Low plasma levels of TSP1 after PCI are associated with MACE. Due to
its procoagulant effects and dysregulation of microvascular tone, adequately
powered prospective studies are warranted to test the impact of TSP-1 on cardiac
microcirculation, endothelial function and remodeling. TSP-1 might serve as a new
diagnostic and therapeutic approach in cardiovascular disease. |
