Lymphangiogenic therapy prevents cardiac dysfunction by ameliorating inflammation and hypertension
Autor: | Michael W. Nagle, Xian Chen, Brianna LaViolette, William C. Sessa, LouJin Song, Youngwook Ahn, Rachel J. Roth Flach, Frank Voigt, Sabra D Al-Harthy, Terri A. Swanson, Teresa Cunio, Steven C. Kreuser, Arun Shipstone, Casey Ritenour, Hanna Sobon, Katherine Hales, Jincheng Pang, Shoh Asano, Furong Sun, Magalie Boucher, Andrew Robertson |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Mouse Vascular Endothelial Growth Factor C 030204 cardiovascular system & hematology Pharmacology Pathogenesis Mice Random Allocation lymphatic 0302 clinical medicine Fibrosis Medicine Gene Knock-In Techniques Biology (General) cardiac dysfunction General Neuroscience Angiotensin II General Medicine Lymphatic Endothelium Lymphatic system cardiovascular system medicine.symptom Research Article Human hypertension Heart Diseases QH301-705.5 government.form_of_government Science Green Fluorescent Proteins Inflammation General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Renin–angiotensin system endothelial Animals Humans Homeodomain Proteins General Immunology and Microbiology business.industry Sequence Analysis RNA Myocardium Tumor Suppressor Proteins fibrosis Endothelial Cells Cell Biology medicine.disease Mice Inbred C57BL 030104 developmental biology Blood pressure inflammation government business Biomarkers Genome-Wide Association Study |
Zdroj: | eLife, Vol 9 (2020) eLife |
Popis: | 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. |
Databáze: | OpenAIRE |
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