Angiogenic growth factor expression in stroke
Angiogenic growth factors play an essential role in the development and structural integrity of the cerebral vasculature, but their importance in stroke is poorly defined. Stroke prone hypertensive rats (SHRSP), a model for genetic stroke susceptibility, suffer spontaneous stroke and enhanced injury after experimental stroke, at least in part due to abnormal cerebrovascular development. We hypothesized that angiogenic genes in SHRSP may follow unique patterns of expression after experimentally induced stroke. Ribonuclease protection assays were used to determine expression levels of the angiogenic receptor Tie-2 and its ligands in the brain after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in SHRSP, and in control SHR and WKY rats. The expression of Tie-2 and Ang-1, an agonist for Tie-2, dropped markedly after stroke in SHRSP animals (70% and 45%; p<0.05), but not in controls. In addition, enhanced expression of Ang-2, a Tie-2 antagonist, is significantly higher in SHRSP animals (50% versus WKY; p<0.05). Together, these data demonstrate that SHRSP may dramatically downregulate Tie-2 signaling after stroke. This suggests that in stroke prone animals, impairment of Tie-2 signaling contributes to stroke vulnerability.