*5.3. Cell Signalling Pathways Activated by the APJ Receptor*

On one hand, APJ activation leads to the activation of phospholipase Cβ, the phosphatidylinositol-3-kinase (PI3K)/Akt pathways and the Na/H exchanger type 1 and, on the other hand, inhibits adenylyl cyclase and subsequent cyclic adenosine monophosphate production [111,148–151]. Phospholipase Cβ triggers protein kinase C (PKC) and downstream Ras/Raf/MEK/Erk, which together with Akt via mTOR are involved in the activation of P70S6K [152] and the endothelial NO synthase, promoting the release of NO, vascular dilatation, and cell proliferation [149]. The activation of the Na/H exchanger type 1 via PKC in cardiomyocytes is responsible for the dose-dependent increase in in vivo and in vitro myocardial contractility [153]. Moreover, some studies associate APJ activation with inflammation [113,115,134]. Actually, APJ induces the expression of vascular cell adhesion molecule-1 (VCAM-1), MCP-1 and intercellular adhesion molecule-1 (ICAM-1) via the NF-κB and the Jnk signalling pathway [154] (Figure 5).

INTRACELLULAR

**Figure 5.** Molecular and cell signalling pathways of APJ.
