Antithrombotic Effect Of Angiopoietin-like Protein 2

ObjectivesAngiopoietin-like protein 2(ANGPTL2) is an inflammatory factor in coronary atherosclerotic heart disease(CHD). However, a recent study indicated that ANGPTL2 can inhibit platelet aggregation in vitro. The aim of our study was to investigate the expression of ANGPTL2 in patients with acute coronary syndrome(ACS). To observe the correlation between ANGPTL2 and spontaneous reperfusion(SR) of infarct-related arterial. Additionally, we assessed the synergistic antithrombotic effect of ANGPTL2 and tirofiban using in vitro platelet aggregation experiments. Methods(1) We recruited 164 patients with CHD who underwent coronary angiography, including 91 patients with ST segment elevation myocardial infarction(STEMI), 40 with non-ST segment elevation acute coronary syndrome(NSTE-ACS), and 33 with stable angina pectoris(SAP). Inaddition, 34 patients with non–coronary heart disease were considered as the control group. ANGPTL2 concentration in peripheral blood plasma was detected using enzyme-linked immunosorbent assay(ELISA). Immunohistochemistry was used to detect ANGPTL2 expression in the coronary thrombus.(2) 88 patients with STEMI were treated with tirofiban, according to coronary angiography were divided into two groups, those with the SR group(n=43) and those with no spontaneous reperfusion(the NSR group)(n=45) were considered as controls. ANGPTL2 concentration in peripheral blood plasma was detected using ELISA. Western blot analysis was performed to detect ANGPTL2 protein expression in platelets from patients with SR.(3) The effects of ANGPTL2 and tirofiban on platelet inhibition were investigated in response to agonist exposure. Results(1) Plasma ANGPTL2 levels were significant higher in patients with STEMI than in those with NSTE-ACS(32.21 ± 18.80 vs. 5.53 ± 6.52, P < 0.001), SAP(32.21 ± 18.80 vs. 1.07 ± 0.78, P < 0.001), and the controls(32.21 ± 18.80 vs. 1.03 ± 0.66, P < 0.001). Additionally, ANGPTL2 levels were significantly higher in the plasma of patients with NSTE-ACS than in that of patients with SAP(P < 0.001) and controls(P < 0.001).The difference between ANGPTL2 levels in patients with SAP and controls were not statistically significant(P = 0.82). ANGPTL2 was highly expressed in the coronary thrombus.(2) ANGPTL2 levels in patients with SR were significantly higher than that in patients with NSR(37.13±19.49 vs. 26.97±16.91, P < 0.05). ANGPTL2 was highly expressed in platelets of patients with SR(P < 0.05).(3) ANGPTL2 inhibited collagen induced platelet aggregation, and this effect was increased by combination with tirofiban, platelet aggregation was almost completely inhibited. Conclusions(1) The high expression of ANGPTL2 is associated with platelet thrombosis in patients with ACS.(2) There is a positive correlation between ANGPTL2 and SR of the infarct-related artery.(3) ANGPTL2 can synergistically enhance the antithrombotic effect of tirofiban.