Abstract
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.
Highlights
Almost 1 in 2 U.S adults have hypertension, and it is uncontrolled in many patients [1].Despite improved education, public health efforts, and prescribed medications, about30–60% of hypertensive patients cannot achieve an ideal blood pressure
We developed two different kidney-targeting nanoparticles, one a micelle (NP1) and the other a liposome (NP2), with an average diameter of 100 nm and containing Coumarin
While there was little Coumarin 6 dye in the hearts, livers, spleens, lungs, and kidneys in mice receiving free dye or the liposome nanoparticle (NP2), there was a significant amount of fluorescence in the kidneys of mice injected with nanoparticle 1 (NP1), the micelle nanoparticle (Figure 1B)
Summary
30–60% of hypertensive patients cannot achieve an ideal blood pressure. This is unfortunate as a decrease in systolic blood pressure of even 10 mmHg significantly reduces health risks and improves outcomes [2]. Additional treatment options are needed to help this hypertensive population reduce their blood pressure, ideally into the normotensive range. Inflammation, and sodium retention are strongly associated with hypertension [3,4,5]. Inflammation-associated lymphangiogenesis is observed upon acute kidney injury and in chronic inflammatory diseases such as diabetic nephropathy and renal carcinoma [8]. An increase in lymphatics tries to help with the Pharmaceutics 2022, 14, 84.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
