Profilin 1 is associated with markers of platelet reactivity and hypofibrinolysis in chronic coronary syndrome
E Paszek, K Bryniarski, P Szolc, T Rajs, B Nosal, M Kopytek, A Klajmon, J LegutkoAbstract
Background
Circulating profilin 1 (Pfn1), an actin cytoskeleton-associated protein, has been shown to increase in myocardial infarction. Preliminary studies suggest that Pfn1 may affect proliferation in atherosclerosis. The mechanisms behind these observations are unknown. Data on Pfn1 in chronic coronary syndrome (CCS) are very limited.
Purpose
We aimed to evaluate circulating Pfn1 levels and its associations with markers of inflammation, NETosis, fibrinolysis, and platelet reactivity in patients with CCS and significant coronary lesions.
Methods
We enrolled patients with class II/III angina according to the Canadian Cardiovascular Society and at least one angiographically significant coronary lesion of a major epicardial vessel (≥50% diameter stenosis) and 40 age- and sex-matched patients with no significant coronary lesions. We excluded patients with recent atherothrombotic events, percutaneous interventions, or surgery (up to 3 months), acute infection, active malignancy, advanced liver or kidney disease, and those on anticoagulation. We measured Pfn1 using ELISA, along with high-sensitive C-reactive protein, citrullinated histone H3 (citH3), a validated marker of NETosis, plasminogen activator inhibitor 1 (PAI-1), the main inhibitor of fibrinolysis, and platelet reactivity markers: soluble CD40 ligand (sCD40L), and P selectin.
Results
We included 119 patients with a median age of 68 (59–72) years; 73.1% men, 54.6% with multivessel disease (Tab. 1). All patients and controls were taking 75mg acetylsalicylic acid at the time of blood collection. Pfn1 was similar in CCS patients and controls (1.0 [0.7-1.7] vs. 1.1 [0.7-1.4], p=0.82). CCS patients with Pfn1 in the top quartile (Pfn1 >1.7 ng/ml) were less often male (58.6% vs. 77.8%. p=0.04), with no other differences in clinical characteristics, comorbidities, or basic laboratory parameters. Patients on dual antiplatelet therapy (DAPT) were less represented in the group with high Pfn1 as compared with the remainder (20.7% vs. 44.4%, p=0.02), attributable to ticagrelor/prasugrel-based DAPT. Patients on ASA + ticagrelor/prasugrel had 45% lower Pfn1 as compared to those on ASA only (0.6 [0.4-0.9] vs. 1.1 [0.7-1.8] ng/ml, p = 0.0014) and 40% lower as compared with those on the ASA + clopidogrel regimen (0.6 [0.4-0.9] vs. 1.0 [0.7-1.4] ng/ml, p = 0.0096, Fig. 1A). Pfn1 correlated strongly with sCD40L (r = 0.77, p<0.0001, Fig. 1B) and weakly, albeit significantly, with P-selectin (r = 0.21, p=0.02, Fig. 1C) and PAI-1 (r = 0.35, p < 0.0001, Fig. 1D).
Conclusions
This preliminary study is the first to show that in CCS Pfn1 levels are associated with markers of platelet activation and hypofibrinolysis. In line, we observed that potent P2Y12 inhibition may attenuate circulating Pfn1. The robust correlation between Pfn1 and sCD40L could indicate a link between Pfn1 and platelet-driven inflammatory activity. This intriguing notion requires further investigation.Pfn and platelet markers, PAI-1 and DAPTPatient characteristics