Forskolin increases angiogenesis through the coordinated cross-talk of PKA-dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

“…6A; Table 1). This observation is in agreement with a recent report on proangiogenic activity triggered by forskolin through the PI3K, Akt, eNOS pathways in human umbilical vascular ECs (22). The ability of L-NAME to exert a near-complete abolishment of forskolin-triggered calcium entry leads us also to confirm that the PKA-dependent phosphorylation of AA-activated calcium channels probably acts in a permissive way, but it is not activatory by itself (i.e., in the absence of AA).…”

“…Pretreatment of B-TECs with the membrane-permeable PKA inhibitory peptide myristoylated PKI [14][15][16][17][18][19][20][21][22] (10 minutes, 20 μmol/L) completely abolished AA-induced calcium entry in 99% of the cells tested (n = 84; Fig. 1; Table 1), suggesting a critical role of endogenous PKA in the activation of calcium signals by AA.…”

“…PKA regulates eNOS activity through serine phosphorylation, and it has been recently reported that forskolin, a widely used adenylyl cyclase activator, is able to trigger proangiogenic effects through the PI3K, Akt, and eNOS pathways in human umbilical vascular ECs (21,22). In addition, it is worth noting that a number of different endothelial calcium-permeable channels are substrates for PKA phosphorylation, including some members of the transient receptor potential (TRP) superfamily of proteins.…”

Activation of Dopamine D1 Receptors in Dermal Fibroblasts Restores Vascular Endothelial Growth Factor-A Production by These Cells and Subsequent Angiogenesis in Diabetic Cutaneous Wound Tissues

“…39,40 Recent reports indicate that VEGF-A expression is also regulated via the PKA/CREB pathway. 41,42 In the present study, we demonstrate that DA D 1 receptors act specifically through this pathway to phosphorylate CREB, and thereby stimulate VEGF-A production by dHDFs, as the inhibition of PKA by H89 abolishes this effect of DA (Figure 4). This significantly increased VEGF-A production by fibroblasts in the wound microenvironment, in turn, stimulates angiogenesis and subsequently accelerates healing of the diabetic wounds (Figures 1 and 2).…”

Peroxisome proliferator-activated receptors as stimulants of angiogenesis in cardiovascular disease and diabetes

“…[57][58][59] In one study pioglitazone reduced the myocardial infarct size in part via activation of eNOS. 60 PPAR-α activation has also been shown to protect the type 2 diabetic rat myocardium against ischemia-reperfusion injury via the activation of the NO pathway (Table 1, Figure 1).…”