The role of MNK1/2 in cardiovascular remodeling

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We have demonstrated that Mnk1/2 are involved in angiotensin II (AngII)-mediated protein synthesis and hypertrophy, presumably through the activation of translation-initiation in vascular smooth muscle cells (VSMC).In the present study, we showed oxidative stress also potently activated Mnk1/2. Oxidative stress-induced Mnk activation was dependent on Ras, ERK and p38MAP kinase. Mnk1 activated by oxidative stress translocated into the nucleus and co-localized with PML body.The protein expression of Ets-1, a transcription factor, stimulated by PDGF or FGF was abolished in VSMC from Mnk1-/-Mnk2-/-mice, which was independent of mRNA level. Similarly, siRNA against Mnk1/2 significantly decreased AngII-induced Ets-1 protein expression, and osteopontin expression, one of the target genes of Ets-1.These data suggest that Mnk1/2 regulate the expression of a certain proteins at the translational level, and may be potential targets for atherosclerotic vascular diseases. In addition, these data indicate that Mnk1/2 have undefined functions in translational machinery and nucleus.