Stanislawa Bazan-Socha1, Pawel Kuczia2, Daniel P Potaczek3, Lucyna Mastalerz4, Agnieszka Cybulska5, Lech Zareba6, Romy Kremers7, Coenraad Hemker8, Anetta Undas9. 1. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. Electronic address: mmsocha@cyf-kr.edu.pl. 2. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; University Hospital, Allergy and Clinical Immunology Department, Krakow, Poland. Electronic address: kuczia@gmail.com. 3. John Paul II Hospital, Krakow, Poland; Institute of Laboratory Medicine, member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), and the inVIVO Planetary Health, Group of the Worldwide Universities Network (WUN), Philipps-University Marburg, Marburg, Germany. Electronic address: potaczek@staff.uni-marburg.de. 4. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. Electronic address: lmastalerz@wp.pl. 5. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. Electronic address: agnes.cybulski@gmail.com. 6. Faculty of Mathematics and Natural Sciences, University of Rzeszow, Rzeszow, Poland. Electronic address: lzareba@univ.rzeszow.pl. 7. Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands. Electronic address: r.kremers@thrombin.com. 8. Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands. Electronic address: hc.hemker@thrombin.com. 9. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. Electronic address: mmundas@cyf-kr.edu.pl.
Abstract
BACKGROUND: Recently, we have reported that asthma is characterized by prothrombotic blood alterations, which were related to the low-grade inflammatory state. Inflammation, however, may also lead to vascular dysfunction. The aim of this study was to evaluate plasma levels of cellular fibronectin (cFN), a marker of vascular injury in asthmatics, and to analyze their impact on described previously prothrombotic blood alterations. METHODS: In a cross-sectional study, we investigated 164 adult stable asthmatics and 72 matched controls. Plasma cFN was measured using an ELISA. Its relations to inflammation, thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were evaluated. RESULTS: Asthma was associated with 50.1% higher plasma cFN levels as compared with controls (p < 0.001, after adjustment for potential confounders). There was a positive association of cFN with asthma severity and inverse with the FEV1/VC index (β = 0.2 [95%CI:0.13-0.28] and β = -0.15 [95%CI: -0.23 to -0.07], respectively). In asthmatics cFN positively correlated with high-sensitivity C-reactive protein (β = 0.24 [95%CI:0.16-0.32]), fibrinogen (β = 0.13 [95%CI:0.04-0.21]), interleukin-6 (β = 0.23 [95%CI:0.15-0.3]), platelet factor 4 (β = 0.14 [95%CI:0.06-0.21]), plasminogen (β = 0.11 [95%CI:0.04-0.19]) and CLT (β = 0.35 [95%CI:0.28-0.42]). In both groups cFN was related to the endogenous thrombin potential (ETP) (β = 0.51 [95%CI:0.44-0.57], and β = 0.17 [95%CI:0.07-0.27], respectively). Multiple regression models showed that cFN was the most potent independent predictor of both ETP and CLT in asthmatics. CONCLUSION: Presented study is the first to show increased plasma cellular fibronectin in asthma, which is associated with disease severity, inflammation, and prothrombotic blood alterations. This novel observation suggests a previously unknown modulator of prothrombotic plasma properties in asthmatics.
BACKGROUND: Recently, we have reported that asthma is characterized by prothrombotic blood alterations, which were related to the low-grade inflammatory state. Inflammation, however, may also lead to vascular dysfunction. The aim of this study was to evaluate plasma levels of cellular fibronectin (cFN), a marker of vascular injury in asthmatics, and to analyze their impact on described previously prothrombotic blood alterations. METHODS: In a cross-sectional study, we investigated 164 adult stable asthmatics and 72 matched controls. Plasma cFN was measured using an ELISA. Its relations to inflammation, thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were evaluated. RESULTS:Asthma was associated with 50.1% higher plasma cFN levels as compared with controls (p < 0.001, after adjustment for potential confounders). There was a positive association of cFN with asthma severity and inverse with the FEV1/VC index (β = 0.2 [95%CI:0.13-0.28] and β = -0.15 [95%CI: -0.23 to -0.07], respectively). In asthmatics cFN positively correlated with high-sensitivity C-reactive protein (β = 0.24 [95%CI:0.16-0.32]), fibrinogen (β = 0.13 [95%CI:0.04-0.21]), interleukin-6 (β = 0.23 [95%CI:0.15-0.3]), platelet factor 4 (β = 0.14 [95%CI:0.06-0.21]), plasminogen (β = 0.11 [95%CI:0.04-0.19]) and CLT (β = 0.35 [95%CI:0.28-0.42]). In both groups cFN was related to the endogenous thrombin potential (ETP) (β = 0.51 [95%CI:0.44-0.57], and β = 0.17 [95%CI:0.07-0.27], respectively). Multiple regression models showed that cFN was the most potent independent predictor of both ETP and CLT in asthmatics. CONCLUSION: Presented study is the first to show increased plasma cellular fibronectin in asthma, which is associated with disease severity, inflammation, and prothrombotic blood alterations. This novel observation suggests a previously unknown modulator of prothrombotic plasma properties in asthmatics.
Authors: Zunxiang Yan; Kang Zhang; Guibo Wang; Lei Wang; Jingyan Zhang; Zhengying Qiu; Zhiting Guo; Kai Zhang; Jianxi Li Journal: Front Vet Sci Date: 2022-09-20