Phospholipase D2 loss results in increased blood pressure via inhibition of the endothelial nitric oxide synthase pathway.

ABSTRACT: The Phospholipase D (PLD) superfamily is linked to neurological disease, cancer, and fertility, and a recent report correlated a potential loss-of-function PLD2 polymorphism with hypotension. Surprisingly, PLD2 ^-/- mice exhibit elevated blood pressure accompanied by associated changes in cardiac performance and molecular markers, but do not have findings consistent with the metabolic syndrome. Instead, expression of endothelial nitric oxide synthase (eNOS), which generates the potent vasodilator nitric oxide (NO), is decreased. An eNOS inhibitor phenocopied PLD2 loss and had no further effect on PLD2 ^-/- mice, confirming the functional relationship. Using a human endothelial cell line, PLD2 loss of function was shown to lower intracellular free cholesterol, causing up

SUBMITTER: Nelson RK 

PROVIDER: S-EPMC5567230 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature