Lymphangiogenic therapy prevents cardiac dysfunction by ameliorating inflammation and hypertension

• DOI: 10.7554/elife.58376
• Publication Date: 2020-11-17T13:00:22Z
• Authors: LouJin Song; Xian Chen; Terri A Swanson; Brianna LaViolette; Jincheng Pang; Teresa Cunio; Michael W Nagle; Shoh Asano; Katherine Hales; Arun Shipstone; Hanna Sobon; Sabra D Al-Harthy; Youngwook Ahn; Steven Kreuser; Andrew Robertson; Casey Ritenour; Frank Voigt; Magalie Boucher; Furong Sun; William C Sessa; Rachel J Roth Flach
• Keywords: Cardiac Fibrosis; Endothelial Dysfunction; Pathogenesis

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