Post-infarction remodeling is independent of mitogen-activated protein kinase kinase 3 (MKK3)

Our aim was to examine the role of mitogen-activated protein kinase kinase 3 (MKK3) in the development of left ventricular (LV) remodeling following myocardial infarction (MI).

MKK3-null mice were subjected to permanent coronary artery ligation. Twenty-eight days after MI, haemodynamics in male mkk3+/+(WT) and mkk3-/-(KO) littermates were assessed using a pressure-conductance catheter. MI groups were compared to un-operated time-matched WT and KO controls.

MI caused significant LV contractile dysfunction and dilatation which did not differ by genotype. Detailed morphometric analysis of excised hearts confirmed these similar global indices of remodeling and also demonstrated that pathological changes within remote myocardium and scar did not differ between KO and WT hearts.

Despite numerous lines of evidence suggesting MKK3 is the relevant kinase upstream of p38 mitogen-activated protein kinase in LV remodeling these processes can continue in its absence.