| First Author | Hansen KB | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32955439 | Mgi Jnum | J:298643 |
| Mgi Id | MGI:6477042 | Doi | 10.7554/eLife.57553 |
| Citation | Hansen KB, et al. (2020) PTPRG is an ischemia risk locus essential for HCO3(-)-dependent regulation of endothelial function and tissue perfusion. Elife 9:e57553 |
| abstractText | Acid-base conditions modify artery tone and tissue perfusion but the involved vascular-sensing mechanisms and disease consequences remain unclear. We experimentally investigated transgenic mice and performed genetic studies in a UK-based human cohort. We show that endothelial cells express the putative HCO3(-)-sensor receptor-type tyrosine-protein phosphatase RPTPgamma, which enhances endothelial intracellular Ca(2+)-responses in resistance arteries and facilitates endothelium-dependent vasorelaxation only when CO2/HCO3(-) is present. Consistent with waning RPTPgamma-dependent vasorelaxation at low [HCO3(-)], RPTPgamma limits increases in cerebral perfusion during neuronal activity and augments decreases in cerebral perfusion during hyperventilation. RPTPgamma does not influence resting blood pressure but amplifies hyperventilation-induced blood pressure elevations. Loss-of-function variants in PTPRG, encoding RPTPgamma, are associated with increased risk of cerebral infarction, heart attack, and reduced cardiac ejection fraction. We conclude that PTPRG is an ischemia susceptibility locus; and RPTPgamma-dependent sensing of HCO3(-) adjusts endothelium-mediated vasorelaxation, microvascular perfusion, and blood pressure during acid-base disturbances and altered tissue metabolism. |
