Lymphangiogenic therapy prevents cardiac dysfunction by ameliorating inflammation and hypertension.

ELife
LouJin SongRachel J Roth Flach

Abstract

The lymphatic vasculature is involved in the pathogenesis of acute cardiac injuries, but little is known about its role in chronic cardiac dysfunction. Here, we demonstrate that angiotensin II infusion induced cardiac inflammation and fibrosis at 1 week and caused cardiac dysfunction and impaired lymphatic transport at 6 weeks in mice, while co-administration of VEGFCc156s improved these parameters. To identify novel mechanisms underlying this protection, RNA sequencing analysis in distinct cell populations revealed that VEGFCc156s specifically modulated angiotensin II-induced inflammatory responses in cardiac and peripheral lymphatic endothelial cells. Furthermore, telemetry studies showed that while angiotensin II increased blood pressure acutely in all animals, VEGFCc156s-treated animals displayed a delayed systemic reduction in blood pressure independent of alterations in angiotensin II-mediated aortic stiffness. Overall, these results demonstrate that VEGFCc156s had a multifaceted therapeutic effect to prevent angiotensin II-induced cardiac dysfunction by improving cardiac lymphatic function, alleviating fibrosis and inflammation, and ameliorating hypertension.

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Citations

May 25, 2021·Current Opinion in Nephrology and Hypertension·Michael D Donnan
Jun 24, 2021·Nature Reviews. Nephrology·Michael D DonnanSusan E Quaggin
Aug 18, 2021·The Journal of Clinical Investigation·T C Stevenson KellerMark L Kahn

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Methods Mentioned

BETA
ELISA
RNA-seq
flow cytometry
biopsies
transgenic
PCR
dissection
protein assay
electrophoresis
FACS

Software Mentioned

QuantStudio 7
sva
Ensembl
DESeq2
Visiopharm
bcl2fastq
FastQC
voom
Salmon
MSD discovery workbench

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