Mitogen-activated protein kinases are
serine-threonine protein kinases that are involved in several processes important to cardiac surgery such as vascular permeability,
cytokine production, vasomotor function, and
reperfusion injury.
Mitogen-activated protein kinases are expressed in multiple cell types including cardiomyocytes, vascular endothelial cells, and vascular smooth muscle cells.
Mitogen-activated protein kinases function in cellular signal transduction cascades and are activated by a diverse range of stimuli including
ischemia, shear stress, and vasoactive agents. Three major
mitogen-activated protein kinase families were identified as the
extracellular signal-regulated kinases, c-Jun NH(2)-terminal
protein kinases, and p38
kinases. Extensive investigation has established roles for
extracellular signal-regulated kinases, c-Jun NH(2)-terminal
protein kinases, and p38
kinases in cardiovascular signal transduction pathways. Activity of these signal cascades may contribute to the increased pulmonary vascular permeability and
myocardial reperfusion injury observed after cardiac surgery with
cardioplegia and
cardiopulmonary bypass. Recent findings from our laboratory suggest that alterations in the activity of myocardial
extracellular signal-regulated kinase pathways occur as a result of
cardioplegia-
cardiopulmonary bypass in humans. In addition, these differences in
extracellular signal-regulated kinase activity were shown to mediate coronary microcirculatory dysfunction associated with
cardioplegia-
cardiopulmonary bypass. The resulting deficit in coronary microcirculatory regulation may potentially lead to detrimental effects on organ perfusion and function. As
mitogen-activated protein kinase pathways are further characterized, our potential to develop methods to prevent morbidity associated with cardiac surgery and
cardiopulmonary bypass may be greatly improved.