TY - JOUR TI - Lymphangiogenic therapy prevents cardiac dysfunction by ameliorating inflammation and hypertension AU - Song, LouJin AU - Chen, Xian AU - Swanson, Terri A AU - LaViolette, Brianna AU - Pang, Jincheng AU - Cunio, Teresa AU - Nagle, Michael W AU - Asano, Shoh AU - Hales, Katherine AU - Shipstone, Arun AU - Sobon, Hanna AU - Al-Harthy, Sabra D AU - Ahn, Youngwook AU - Kreuser, Steven AU - Robertson, Andrew AU - Ritenour, Casey AU - Voigt, Frank AU - Boucher, Magalie AU - Sun, Furong AU - Sessa, William C AU - Roth Flach, Rachel J A2 - Barton, Matthias A2 - Koh, Gou Young A2 - Koh, Gou Young VL - 9 PY - 2020 DA - 2020/11/17 SP - e58376 C1 - eLife 2020;9:e58376 DO - 10.7554/eLife.58376 UR - https://doi.org/10.7554/eLife.58376 AB - 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. KW - lymphatic KW - endothelial KW - cardiac dysfunction KW - inflammation KW - hypertension KW - fibrosis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -