A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice
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 hyperten...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/1/84 |
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| author | Bethany L. Goodlett Chang Sun 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 Brett M. Mitchell |
| author_facet | Bethany L. Goodlett Chang Sun 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 Brett M. Mitchell |
| author_sort | Bethany L. Goodlett |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:42:47Z |
| format | Article |
| id | doaj.art-0a0fdc36837b49b6852e2b32aa7824d6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T00:42:47Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0a0fdc36837b49b6852e2b32aa7824d62023-11-23T15:03:36ZengMDPI AGPharmaceutics1999-49232021-12-011418410.3390/pharmaceutics14010084A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive MiceBethany L. Goodlett0Chang Sun Kang1Eunsoo Yoo2Shobana Navaneethabalakrishnan3Dakshnapriya Balasubbramanian4Sydney E. Love5Braden M. Sims6Daniela L. Avilez7Winter Tate8Delilah R. Chavez9Gaurav Baranwal10Mary B. Nabity11Joseph M. Rutkowski12Dongin Kim13Brett M. Mitchell14Department of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Science, Texas A&M University, College Station, TX 77843, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USADepartment of Medical Physiology, College of Medicine, Texas A&M University, Bryan, TX 77807, USAChronic 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.https://www.mdpi.com/1999-4923/14/1/84kidneylymphaticsinflammationimmunityhypertension |
| spellingShingle | Bethany L. Goodlett Chang Sun 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 Brett M. Mitchell A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice Pharmaceutics kidney lymphatics inflammation immunity hypertension |
| title | A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice |
| title_full | A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice |
| title_fullStr | A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice |
| title_full_unstemmed | A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice |
| title_short | A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice |
| title_sort | kidney targeted nanoparticle to augment renal lymphatic density decreases blood pressure in hypertensive mice |
| topic | kidney lymphatics inflammation immunity hypertension |
| url | https://www.mdpi.com/1999-4923/14/1/84 |
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