Cardiovascular and hemodynamic failure

Bruxelles Woluwe

Sepsis is one of the world's 10 leading causes of death. The cardiovascular system is directly affected by the occurrence of sepsis. On one hand, a myocardial depression, defined as a reversible impairment of cardiac function, occurs in 50% of cases, on the other hand, an endothelial dysfunction, characterized by an increase of the permeability of the vessels and an increase in the expression of adhesion and coagulation molecules, induces a prothrombogenic state.

We have shown that α1AMPK (AMP-activated kinase) is involved in sepsis. AMPK is a protein kinase constituted by a catalytic subunit (α1 and α2 isoforms) and regulatory subunits (β and γ). AMPK is involved in the control of cellular metabolism but its role also extends to cytoskeletal control, intercellular junctions or inflammation.

We have shown that mice with a knocked down AMPH subunit gene, show a decrease in sepsis tolerance compared to wild-type mice despite an identical production of systemic cytokines. A significant increase in vascular permeability, particularly in the myocardium, in response to sepsis has been demonstrated. This increase of endothelial dysfunction could extend beyond vascular permeability and participate in organ failure.

The aim of our research is to study the role of endothelial 1AMPK in vascular dysfunctions and hemostatic disorders during sepsis. Our hypothesis is that the 1AMPK subunit of the endothelial cells is involved on one hand in the occurrence of arterial hypotension following sepsis and secondary mortality and on the other hand in the mechanisms leading to a prothrombogenic state. This project is carried out in the Cardiovascular Pathology Laboratory.