Wnt signaling, a novel pathway regulating blood pressure? State of the art review.

Recent antihypertensive trials show conflicting results on blood pressure (BP) targets in patient populations with different metabolic profiles, with lowest benefit from tight BP control observed in patients with type 2 diabetes mellitus. This paradox could arise from the heterogeneity of study populations and underscores the importance of precision medicine initiatives towards understanding and treating hypertension. Wnt signaling pathways and genetic variations in its signaling peptides have been recently associated with metabolic syndrome, hypertension and diabetes, generating a breakthrough for advancement of precision medicine in the field of hypertension. We performed a review of PubMed for publications addressing the contributions of Wnt to BP regulation and hypertension. In addition, we performed a manual search of the reference lists for relevant articles, and included unpublished observations from our laboratory. There is emerging evidence for Wnt's role in BP regulation and its involvement in the pathogenesis of hypertension. Wnt signaling has pleiotropic effects on distinct pathways that involve vascular smooth muscle plasticity, and cardiac, renal, and neural physiology. Hypertension is a heterogeneous disease with unique molecular pathways regulating its response to therapy. Recognition of these pathways is a prerequisite to identify novel targets for drug development and personalizing medicine. A review of Wnt signaling reveals its emerging role in BP regulation and as a target for novel drug development that has the potential to transform the therapy of hypertension in specific populations.