Changes in various forms of fibronectin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass - a prospective, observational study

Abstract

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) is associated with the transient activation of a systemic inflammatory response. Fibronectin (FN), an endogenous inflammatory mediator, is a key component of the extracellular matrix. This study aimed to detect changes in cellular and plasma FN levels, as well as its potential fragmentation or FN-fibrin complex formation, in 40 patients undergoing CABG with CPB. Our results indicate that CPB was associated with changes in the levels of cellular and plasma FN and with intensified FN fragmentation. Moreover, FN-fibrin complexes were detected in all patients, indicating activation of the coagulation process during CPB. In a multivariate regression analysis, a history of arterial hypertension and CPB duration influenced plasma FN levels at 6 h (β = -0.458, p = 0.001; -0.375, p = 0.008, respectively) and 12 h (β = -0.293, p = 0.026; -0.554, p = 0.000) after surgery. Alterations in FN concentration, intensified FN degradation, and the presence of FN-fibrin complexes after surgery may suggest that these changes are related to the remodelling of the extracellular matrix resulting from cardiac surgery and the associated repair processes. The results indicate that FN has clinical potential as a marker of repair processes.

Keywords: Cardiopulmonary bypass; EDA-FN; FN-fibrin complexes; Fibronectin; Inflammation.

Fig. 1

Box plots showing the changes in pFN (A) and EDA-FN (B) levels from baseline, measured at subsequent time points: 0 (baseline, after the induction of anaesthesia but 30 min. before starting the procedure, baseline level), and at 3, 6, 12, and 24 h of reperfusion after re-establishing coronary circulation. Box plots show minimum and maximum values (whiskers), median (middle point), and interquartile range (box).

Fig. 2

Box plots showing the changes in biomarker levels from baseline, measured at subsequent time points: 0 h (baseline, after the induction of anesthesia, but 30 min before starting the procedure), and at 3, 6, 12 and 24 h after reperfusion and re-establishment of coronary circulation. Box plots show minimum and maximum (whiskers), median (middle point), and interquartile range (box).

Fig. 3

Immunological patterns of fibronectin (FN) forms and their corresponding densitograms in representative blood plasma samples from patient and a healthy volunteer. The plasma sample was subjected to SDS (7.5%)-polyacrylamide gel electrophoresis and Western blotting as described in the “Materials and Methods” section. The densitogram of the obtained pattern was analysed using Gene Tools from the Syngene program. Rf distance - the migration distance of the protein through the gel divided by the migration distance of the dye front.

Fig. 4

A comparison of the relative amounts of fibronectin (FN) fragments ~ 160 kDa (A) and ~ 200 kDa (B) in patients (baseline) and healthy volunteers. The box plots show minimum and maximum values (whiskers), median (middle point), and interquartile ranges (box).

Fig. 5

Box plots showing the changes in relative amounts of high-mass FN band (> 230 kDa, representing the fibronectin-fibrin complex) from baseline, measured at subsequent time points: 0 h (baseline, after the induction of anesthesia, but 30 min before starting the procedure), and at 3, 6, 12 and 24 h after reperfusion and re-establishment of coronary circulation. Box plots show minimum and maximum values (whiskers), median (middle point), and interquartile ranges (box).