| First Author | Lupieri A | Year | 2020 |
| Journal | J Cell Sci | Volume | 133 |
| Issue | 13 | PubMed ID | 32482794 |
| Mgi Jnum | J:292631 | Mgi Id | MGI:6448622 |
| Doi | 10.1242/jcs.245969 | Citation | Lupieri A, et al. (2020) A non-catalytic function of PI3Kgamma drives smooth muscle cell proliferation after arterial damage. J Cell Sci 133(13):jcs245969 |
| abstractText | Arterial remodeling in hypertension and intimal hyperplasia involves inflammation and disrupted flow, both of which contribute to smooth muscle cell dedifferentiation and proliferation. In this context, our previous results identified phosphoinositide 3-kinase gamma (PI3Kgamma) as an essential factor in inflammatory processes of the arterial wall. Here, we identify for the first time a kinase-independent role of nonhematopoietic PI3Kgamma in the vascular wall during intimal hyperplasia using PI3Kgamma-deleted mice and mice expressing a kinase-dead version of the enzyme. Moreover, we found that the absence of PI3Kgamma in vascular smooth muscle cells (VSMCs) leads to modulation of cell proliferation, associated with an increase in intracellular cAMP levels. Real-time analysis of cAMP dynamics revealed that PI3Kgamma modulates the degradation of cAMP in primary VSMCs independently of its kinase activity through regulation of the enzyme phosphodiesterase 4. Importantly, the use of an N-terminal competing peptide of PI3Kgamma blocked primary VSMC proliferation. These data provide evidence for a kinase-independent role of PI3Kgamma in arterial remodeling and reveal novel strategies targeting the docking function of PI3Kgamma for the treatment of cardiovascular diseases. |
