Receptor and nonreceptor tyrosine kinases in vascular biology of hypertension.
OBJECTIVE
Extensive evidence indicates that receptor tyrosine kinases and nonreceptor tyrosine kinases underlie vascular damage in hypertension. However, recent clinical studies using vascular endothelial growth factor (VEGF) receptor inhibitors (bevacizumab, axitinib) revealed the unexpected finding of increased blood pressure. Whether this is a generalized receptor tyrosine kinase phenomenon or a VEGF receptor-specific effect is unclear. The present review focuses on current findings regarding the role of tyrosine kinases and signaling in vascular pathobiology of hypertension.


RESULTS
Multiple complex and interacting signaling pathways activated by receptor and nonreceptor tyrosine kinases are upregulated and have been implicated in vascular alterations associated with high blood pressure. Experimental evidence suggests that receptor tyrosine kinase activation by direct ligand binding as well as by ligand-independent mechanisms through transactivation by G protein-coupled receptors plays a role in vascular signaling and cardiovascular diseases.


CONCLUSIONS
Cellular mechanisms and signaling pathways mediated by tyrosine kinases involved in hypertensive vascular damage are currently the subject of intensive investigation. The unexpected finding of hypertension as a side effect in patients treated with VEGF receptor inhibitors suggests that some tyrosine kinases negatively regulate vascular function. Further characterization of these processes will provide greater understanding of the role of tyrosine kinases in vascular pathobiology in hypertension and should provide new insights on novel therapeutic targets.
Yogi
Alvaro
A
Kidney Research Center, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. yalvaro@uottawa.ca
O'Connor
Sarah E
SE
Callera
Glaucia E
GE
Tostes
Rita C
RC
Touyz
Rhian M
RM
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases