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

1
Department of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USA
2
Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USA
3
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Science, Texas A&M University, College Station, TX 77843, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Francisco Javier De La Mata
Pharmaceutics 2022, 14(1), 84; https://doi.org/10.3390/pharmaceutics14010084
Received: 4 November 2021 / Revised: 7 December 2021 / Accepted: 27 December 2021 / Published: 30 December 2021
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. View Full-Text
Keywords: kidney; lymphatics; inflammation; immunity; hypertension kidney; lymphatics; inflammation; immunity; hypertension
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MDPI and ACS Style

Goodlett, B.L.; Kang, C.S.; Yoo, E.; Navaneethabalakrishnan, S.; Balasubbramanian, D.; Love, S.E.; Sims, B.M.; Avilez, D.L.; Tate, W.; Chavez, D.R.; Baranwal, G.; Nabity, M.B.; Rutkowski, J.M.; Kim, D.; Mitchell, B.M. A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice. Pharmaceutics 2022, 14, 84. https://doi.org/10.3390/pharmaceutics14010084

AMA Style

Goodlett BL, Kang CS, Yoo E, Navaneethabalakrishnan S, Balasubbramanian D, Love SE, Sims BM, Avilez DL, Tate W, Chavez DR, Baranwal G, Nabity MB, Rutkowski JM, Kim D, Mitchell BM. A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice. Pharmaceutics. 2022; 14(1):84. https://doi.org/10.3390/pharmaceutics14010084

Chicago/Turabian Style

Goodlett, Bethany L., Chang S. Kang, Eunsoo Yoo, Shobana Navaneethabalakrishnan, Dakshnapriya Balasubbramanian, Sydney E. Love, Braden M. Sims, Daniela L. Avilez, Winter Tate, Delilah R. Chavez, Gaurav Baranwal, Mary B. Nabity, Joseph M. Rutkowski, Dongin Kim, and Brett M. Mitchell. 2022. "A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice" Pharmaceutics 14, no. 1: 84. https://doi.org/10.3390/pharmaceutics14010084

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