Faculty Collaboration Database

Chromosome 2 Fragment Substitutions in Dahl Salt-Sensitive Rats and RNA Sequencing Identified Enpep and Hs2st1 as Vascular Inflammatory Modulators. Hypertension 2021 Jan;77(1):178-189

Date

11/10/2020

Pubmed ID

33161775

Pubmed Central ID

PMC7726001

DOI

10.1161/HYPERTENSIONAHA.120.15690

Scopus ID

2-s2.0-85097833482 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (SS-chromosome 2^BN/Mcwi; consomic S2^B) reduced blood pressure and vascular inflammation under a normal-salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce blood pressure and vascular inflammation in rats fed NSD or high-salt diet (HSD). Four- to 6-week old male SS and congenic rats containing the BN chromosome 2 distal portion (SS.BN-[rs13453786-rs66377062]/Aek; S2^Ba) and middle segment (SS.BN-[rs106982173-rs65057186]/Aek; S2^Bb) were fed NSD or HSD (4% NaCl) up to age 12 to 13 weeks. Systolic blood pressure determined by telemetry was higher in SS rats fed HSD versus NSD. Systolic blood pressure was lower in both congenic rats than in SS under NSD, but similar under HSD versus SS. Reactive oxygen species generation using dihydroethidium staining, expression of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, and immune cell infiltration by immunofluorescence demonstrated that S2^Ba rats present less inflammation under NSD and more under HSD versus SS rats. RNA sequencing and reverse transcription-quantitative PCR identified 2 differentially expressed genes encoded within BN chromosome 2 distal portion that could act as regulators of vascular inflammation. These were downregulated glutamyl aminopeptidase (Enpep) that was anti-inflammatory under NSD and upregulated heparan sulfate 2-O-sulfotransferase 1 (Hs2st1) that was proinflammatory under HSD. In conclusion, 2 differentially expressed genes encoded within introgressed BN chromosome 2 distal fragment were identified: Enpep associated with reduced vascular inflammation under NSD, and Hs2st1, associated with increased vascular inflammation under HSD.

Author List

Berillo O, Ouerd S, Idris-Khodja N, Rehman A, Richer C, Sinnett D, Kwitek AE, Paradis P, Schiffrin EL

Author

Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chromosomes, Mammalian
Glutamyl Aminopeptidase
Humans
Hypertension
Male
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Sequence Analysis, RNA
Sodium Chloride, Dietary
Sulfotransferases
Vasculitis