Mice lacking the Raf-1 kinase inhibitor protein exhibit exaggerated hypoxia-induced pulmonary hypertension.

ABSTRACT:

Background and purpose

Increased pulmonary vascular remodelling, pulmonary arterial pressure and pulmonary vascular resistance characterize the development of pulmonary arterial hypertension (PAH). Activation of the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)1/2 is thought to play an important role in PAH and Raf-1 kinase inhibitor protein (RKIP), negatively regulates this pathway. This study investigated whether genetic deletion of RKIP (and hence ERK1/2 up-regulation) resulted in a pulmonary hypertensive phenotype in mice and investigated a role for RKIP in mitogen-regulated proliferative responses in lung fibroblasts.

Experimental approach

Pulmonary vascular haemodynamics and remodelling were assessed in mice genetically deficient in R

SUBMITTER: Morecroft I 

PROVIDER: S-EPMC3130942 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature