Factor XIII-A dynamics in acute myocardial infarction: a novel prognostic biomarker?

Abstract

After acute myocardial infarction (MI) the damaged heart has to be repaired. Factor XIII (FXIII) is considered a key molecule in promoting heart healing. FXIII deficiency was associated to cardiac rupture and anomalous remodelling in MI. During MI, FXIII contributes firstly to the intracoronary thrombus formation and shortly after to heal the myocardial lesion. To quantify the real contribution of FXIII in this process, and to explore its possible prognostic role, we monitored the FXIII-A subunit levels in 350 acute MI patients during the first six days (d0-d5) plus a control at 30-60 days (d30). A one-year follow-up was performed for all the patients. A transient drop in the FXIII-A mean level was noted in the whole cohort of patients (FXIII-Ad0 99.48 ± 30.5 vs FXIII-Ad5 76.51 ± 27.02; p< 0.0001). Interestingly, those who developed post-MI heart failure showed the highest drop (FXIII-Ad5 52.1 ± 25.2) and they already presented with low levels at recruitment. Similarly, those who died showed the same FXIII-A dynamic (FXIII-Ad5 54.0 ± 22.5). Conversely, patients who remained free of major adverse cardiac events, had lower consuming (FXIII-Ad0 103.6 ± 29.1 vs FXIII-Ad5 84.4 ± 24.5; p< 0.0001). Interestingly, the FXIII-A drop was independent from the amount of injury assessed by TnT and CKMB levels. The survival analysis ascribed an increased probability of early death or heart failure inversely related to FXIII-A quartiles (FXIII-A25th< 59.5 %; hazard ratio 4.25; 2.2-5.1; p< 0.0001). Different FXIII-A dynamics and levels could be utilised as early prognostic indicators during acute MI, revealing the individual potential to heal and suggesting tailored treatments to avoid heart failure or its extreme consequence.

Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective

“…The past few decades of research have shown FXIII to have multiple pleiotropic functions 12 . It is known to play roles in maintaining vascular permeability, in development of extracellular matrix in bone and cartilage, in fostering cardioprotective effects, as a first line of defense against invading pathogens and, as recently reported, in pre-adipocyte differentiation and arthritis 13 14 15 16 17 18 . Identification and cloning of the F13A1 and F13B genes, along with the recombinant expression of the FXIIIA 2 and B 2 subunits 19 20 21 , was followed by high-resolution structural determination of the FXIIIA 2 dimer in zymogenic forms 22 23 24 25 .…”

Fibrinogen and factor XIII: newly recognized roles in venous thrombus formation and composition

“…Finally, it is clear that many biologic functions of FXIII have not been thoroughly elucidated. In addition to coagulation, FXIII may have roles in arthritis(50), adipogenesis(51), and cardiac repair(52, 53). It will be important to understand the impact of FXIII inhibition on these situations before the benefit of a FXIIIa antagonist can be realized in the clinic.…”

Association of factor XIII Val34Leu polymorphism and coronary artery disease: A meta-analysis

“…Moreover, the proangiogenic function of factor XIII is directed by the interaction of vascular endothelial growth factor receptor 2 and integrin aVb 3 on the cell membrane [51]. Certain studies showed that low factor XIIIA level correlated with a poor prognosis with regard to MI [52,53]. Therefore, MI could be differently affected by this function of factor XIII compared to CAD without MI.…”