El factor de crecimiento del hepatocito disminuye la expresión vascular de mediadores inflamatorios y la hipertensión en ratas espontáneamente hipertensas

Objective

This study was designed to examine the effects of hepatocyte growth factor (HGF) gene delivery on vascular inflammation and hypertension in spontaneously hypertensive rats (SHR). We speculated that HGF deficiency could play a key role in the pathogenesis of hypertension in SHR, and that increasing HGF levels will produce prolonged decreases in blood pressure due to reduced vascular inflammation.

Materials and methods

Fifteen-week old male SHRs received weekly hydrodynamic injections of a naked plasmid containing human HGF (pCMV-HGF) (1 mg/kg) or empty vector (pcDNA3.1) for 6 weeks. Two groups of Wistar-Kyoto (WKY) rats were used as controls (n = 6) and treated in the same manner. The activation of NF-κB was assessed by Western blot and mRNA expression of pro-inflammatory cytokines by real-time PCR and Western blot.

Results

Blood pressure, NF-κB activation and expression of IL-6, MCP-1 and RANTES were significantly higher in SHR than in the control WKY. The HGF gene therapy normalized NF-κB activity, pro-inflammatory cytokines expression, and decreased the hypertension in SHR.

Conclusion

These observations suggest that decreased aorta HGF concentration may have a role in the vascular inflammation observed in SHR, and demonstrate that increasing HGF is a potential therapeutic target in the treatment of hypertension.