Endothelin-1 overexpression in mice increases vascular Vegfa164 and Vegfa188 alternative splice isoforms via enhanced Khdrbs3 expression

Berillo, Olgaa

doi:10.1097/HJH.0000000000004363

Endothelin-1 overexpression in mice increases vascular Vegfa164 and Vegfa188 alternative splice isoforms via enhanced Khdrbs3 expression

2026-06-09

0

PRE

AI

B

Berillo, Olgaa

C

Coelho, Suellen C.a

F

Ferreira, Nathanne S.a

R

Richer, Chantalc

S

Sinnett, Danielc, d

P

Paradis, Pierrea

S

Schiffrin, Ernesto L.a, b

DOI：10.1097/HJH.0000000000004363

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Abstract

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Mice with tamoxifen-inducible endothelium-restricted human endothelin-1 (ET-1) overexpression (ieET-1) exhibited blood pressure elevation after 3 weeks and 3 months, and vascular injury after 3 months. We hypothesised that ET-1 overexpression-induced vascular injury is mediated by gene expression dysregulation.

Keywords:

hypertension

RNA sequencing

RNA splicing

vascular injury

Ang II

angiotensin II

ANOVA

analysis of variance

Aqp1

mouse aquaporin-1 gene

BP

blood pressure

Cacna1c

rat voltage-dependent L-type calcium channel subunit alpha-1C gene

CAG

cytomegalovirus enhancer/chicken β-actin promoter

cat

chloramphenicol acetyltransferase gene

CaV1.2<sub xmlns:mrws="http://webservices.ovid.com/mrws/1.0">1C</sub>

voltage-dependent L-type calcium channel subunit alpha-1C

CD

cluster of differentiation

Cd36

mouse CD36 gene

CKD

chronic kidney disease

CMV

cytomegalovirus

CNN1

human calponin 1gene

Col13a1

mouse collagen type XIII alpha 1 chain gene

CTD

Comparative Toxicogenomic s Database

Cyp11a1

mouse cytochrome P450 family 11 subfamily A member 1 gene

DCM

dilated cardiomyopathy

EDN1 and Edn1

human and mouse endothelin gene

eET-1

endothelial endothelin-1

Ehf

mouse ETS homologous factor gene

Eln

mouse elastin gene

ET

Endothelin

FDR

false discovery rate

GO

gene ontology

GPI

glycosylphosphatidyl-inositol

HgCl<sub xmlns:mrws="http://webservices.ovid.com/mrws/1.0">2</sub>

mercury chloride

Hsd3b1

mouse hydroxy-delta-5-steroid dehydrogenase

3 beta- and steroid delta-isomerase 1 gene

ieCre

tamoxifen-inducible endothelial-restricted Cre recombinase

ieET-1

tamoxifen-inducible endothelial-restricted human endothelin-1 overexpressing

KHDRBS3

Khdrbs3 and khdrbs3

human

mouse and zebra fish KH domain containing RNA binding signal transduction associated 3 gene

KHDRBS3

KHDRBS3 protein

Ly6e

mouse lymphocyte antigen 6 family member e gene

mRNA

messenger RNA

MYH11

human smooth muscle myosin heavy chain gene

ncRNAs

non-coding RNAs

Pdpn

mouse podoplanin gene

Pon1

mouse paraoxonase 1 gene

r

Pearson Product Moment Correlation coefficient

Rbfox2

rat RNA binding Fox-1 homolog 2 gene

RBFOX2

RNA binding Fox-1 homolog 2 protein

Rgs5

mouse regulator of G protein signaling 5 gene

RIG-E

retinoic acid-induced gene E

RT-qPCR

reverse transcription-quantitative PCR

Sam68

Src-associated in mitosis

68 kDa

SCA-2

Stem Cell Antigen-2

seq

sequencing

SML-2 or SLM2

Sam68-like protein 2

SMTN

human smoothelin gene

SNP

single nucleotide polymorphisms

Star

mouse steroidogenic acute regulatory protein gene

STAR

signal transduction and activation RNA

TAGLN

human transgelin

also known as smooth muscle protein 22-alpha gene

Tek and Tie2

angiopoietin-1 receptor gene

TSA1

Thymic Shared Antigen-1

T-STAR

testis-signal transduction and activation of RNA

uPAR

urokinase-type plasminogen activator receptor

VEGFA and Vegfa

human and mouse vascular endothelial growth factor A gene

VEGFA

VEGFA protein

VEGFR

VEGF receptor

VSMCs

vascular smooth muscle cells

Endothelin-1 overexpression in mice increases vascular Vegfa164 and Vegfa188 alternative splice isoforms via enhanced Khdrbs3 expression

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