Clark James E, Flavell Richard A, Faircloth Matthew E, Davis Roger J, Heads Richard J, Marber Michael S
The Cardiovascular Division, Kings College London, The Rayne Institute, St Thomas' Hospital, London, UK.
Cardiovasc Res. 2007 Jun 1;74(3):466-70. doi: 10.1016/j.cardiores.2007.02.027. Epub 2007 Feb 28.
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.
我们的目的是研究丝裂原活化蛋白激酶激酶3（MKK3）在心肌梗死（MI）后左心室（LV）重塑发展中的作用。
将MKK3基因敲除小鼠进行永久性冠状动脉结扎。心肌梗死后28天，使用压力-电导导管评估雄性mkk3+/+(野生型，WT)和mkk3-/-(基因敲除型，KO)同窝小鼠的血流动力学。将心肌梗死组与未手术的时间匹配的野生型和基因敲除型对照组进行比较。
心肌梗死导致显著的左心室收缩功能障碍和扩张，且在不同基因型之间无差异。对切除心脏的详细形态计量分析证实了这些相似的整体重塑指标，并且还表明基因敲除型和野生型心脏之间，远隔心肌和瘢痕内的病理变化没有差异。
尽管有大量证据表明MKK3是左心室重塑中p38丝裂原活化蛋白激酶上游的相关激酶，但在其缺失的情况下，这些过程仍可继续。
