Decreased TSP-1 following percutaneous coronary intervention is associated with major adverse cardiac events in ST-elevation myocardial infarction

Abstract

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.

The role of circulating thrombospondin-1 in patients with precapillary pulmonary hypertension

“…Furthermore, the vascular endothelium might not be the only source of TSP-1 in PH, as increasing right ventricular load might release TSP-1 from cardiomyocytes as hemodynamics deteriorate. The release of TSP-1 from the myocardium especially due to ischemia-reperfusion injury has been shown previously [ 19 ] and might limit specificity of TSP-1 as a marker for diagnosis of PH.…”

Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction

“…Previous studies showed conflicting evidence of TSP-1 during AMI. One study reported that TSP-1 could have a protective role in preventing the expansion of healing myocardial infarcts [ 24 ], but another stated that low TSP-1 could be associated with major adverse cardiac events in ST-elevation myocardial infarction [ 25 ]. Befekadu et al [ 26 ] found TSP-1 rapidly declined after P CI even significantly lower than in healthy individuals.…”

Association of Atrial Arrhythmias With Thrombospondin-1 in Patients With Acute Myocardial Infarction

“…Previous studies showed conflicting evidence of TSP-1 during AMI. One study reported that TSP-1 could have a protective role in preventing the expansion of healing myocardial infarcts [22], but another stated that low TSP-1 could be associated with major adverse cardiac events in ST-elevation myocardial infarction [23]. Befekadu et al [24] found TSP-1 rapidly declined after PCI, even significantly lower than in healthy individuals.…”