A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice

Goodlett, Bethany L. and Kang, Chang Sun and Yoo, Eunsoo and Navaneethabalakrishnan, Shobana and Balasubbramanian, Dakshnapriya and Love, Sydney E. and Sims, Braden M. and Avilez, Daniela L. and Tate, Winter and Chavez, Delilah R. and Baranwal, Gaurav and Nabity, Mary B. and Rutkowski, Joseph M. and Kim, Dongin and Mitchell, Brett M. (2021) A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice. Pharmaceutics, 14 (1). p. 84. ISSN 1999-4923

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Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice. We hypothesized that targeted nanoparticle delivery of vascular endothelial growth factor-C (VEGF-C) to the kidney would induce renal lymphangiogenesis, lowering blood pressure in hypertensive mice. A kidney-targeting nanoparticle was loaded with a VEGF receptor-3-specific form of VEGF-C and injected into mice with angiotensin II-induced hypertension or LNAME-induced hypertension every 3 days. Nanoparticle-treated mice exhibited increased renal lymphatic vessel density and width compared to hypertensive mice injected with VEGF-C alone. Nanoparticle-treated mice exhibited decreased systolic blood pressure, decreased pro-inflammatory renal immune cells, and increased urinary fractional excretion of sodium. Our findings demonstrate that pharmacologically expanding renal lymphatics decreases blood pressure and is associated with favorable alterations in renal immune cells and increased sodium excretion.

Item Type: Article
Uncontrolled Keywords: kidney; lymphatics; inflammation; immunity; hypertension
Subjects: Euro Archives > Medical Science
Depositing User: Managing Editor
Date Deposited: 11 Nov 2022 04:35
Last Modified: 11 Nov 2022 04:35
URI: http://euroarchives.uk/id/eprint/96

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