Key Points
- To determine whether spleen tyrosine kinase is expressed in vascular smooth muscle cells and delineate its role and signaling mechanism in angiotensin II-induced protein synthesis.
- Treated rat vascular smooth muscle cells with angiotensin II, arachidonic acid, and selective pharmacological inhibitors of phospholipase, lipoxygenase, cyclooxygenase, p38 MAPK, and c-Src.
- Inoculated cells with dominant-negative mutants of Syk, p38 MAPK, and c-Src, or retrovirus carrying shRNA against cytosolic phospholipase A2 to evaluate phosphorylation cascades.
- Assessed vascular smooth muscle cell protein synthesis following angiotensin II stimulation in the presence of a dominant-negative Syk mutant and an epidermal growth factor receptor blocker.
- Angiotensin II induced spleen tyrosine kinase phosphorylation through the AT1 receptor via a sequential cPLA2, lipoxygenase-derived arachidonic acid metabolite, p38 MAPK, and c-Src signaling cascade.
- Inhibition of cytosolic phospholipase A2, lipoxygenase, p38 MAPK, or c-Src attenuated Syk phosphorylation, whereas cyclooxygenase inhibition had no effect.
- Expression of a dominant-negative Syk mutant abolished angiotensin II-induced protein synthesis without requiring epidermal growth factor receptor transactivation.
Structured PICO
PPopulationRat vascular smooth muscle cells (VSMC)
IInterventionAngiotensin II (Ang II) stimulation
OOutcomeSyk phosphorylation and protein synthesissurrogate
This study elucidates the signaling pathway by which Angiotensin II activates Syk to induce protein synthesis in vascular smooth muscle cells, highlighting a potential mechanism in vascular remodeling.