ALTERED ABUNDANCE OF MESSENGER RNA TRANSCRIPTS WHOSE PRODUCTS HAVE MEMBRANE ATTACHMENT SITES IN PREGNANCY-INDUCED HYPERTENSION

Abstract

Pregnancy-induced hypertensive disorders (PIH) are leading causes of maternal mortality. Although the mechanism responsible for initiating and maintaining the disorder is unproven, physiologic molecular attachments in kidney and placenta play a role. The SHHF/Mcc-facp (SHHF) rat has features of the disorder, including abnormal placenta gene expression. To gain a molecular understanding of the gene expression profile associated with PIH, kidneys and placentas of SHHF rats at gestation day 20 were compared to WKY controls using microarray technology. We report that SHHF rats have spontaneous PIH, elevated total placenta weights, and reduced total pup weights than WKY controls and that they also have greater total number of mRNA transcripts expressed in placenta. Kidneys of SHHF rats, on the other hand, not only expressed disproportionately more predicted gene products with attachment sites such as RGD motifs, N-glycosylation sites, and N-myristoylation sites they also responded more profoundly to oral administration of L-arginine. We conclude that the increased abundance of transcripts whose products engage in posttranslational attachments using RGD motifs, N-glycosylation sites, and N-myristoylation sites and the reversal of these increases by oral administration of L-arginine suggests that NO may be of importance in PIH at the level of molecular attachments.