ArticleAmerican journal of nephrology2020
Recovery of Renal Function following Kidney-Specific VEGF Therapy in Experimental Renovascular Disease.
Article in American journal of nephrology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Engineering Kidney-Targeted Drug Delivery Systems: Principles, Materials, and Emerging Strategies.International journal of nanomedicine · 2026Review
- Kidney-specific delivery of a matrix metalloproteinase-2 inhibitory peptide fused to elastin-like polypeptide reduces proteinuria and renal fibrosis in a model of salt-sensitive hypertension.The Journal of pharmacology and experimental therapeutics · 2025Article
- When in doubt, pig it out: a versatile translational platform to study CKD, HFpEF, and CKM syndrome.American journal of physiology. Heart and circulatory physiology · 2025Review
- Multi-lens ultrasound arrays enable large scale three-dimensional micro-vascularization characterization over whole organs.Nature communications · 2025Article
- Kidney health outcomes of hypertensive disorders of pregnancy.Nature reviews. Nephrology · 2025Review
- Renal ischemia alters the mRNA and miRNA profile of vasculature-related genes in scattered tubular-like cells from female pigs.American journal of physiology. Renal physiology · 2025Article
- Microvascular aberrations found in human polycystic kidneys are an early feature in a Pkd1 mutant mouse model.Disease models & mechanisms · 2025Article
- Genetic Functionalization of Protein-Based Biomaterials via Protein Fusions.Biomacromolecules · 2024Review
- Research Progress of Drug Delivery Systems Targeting the Kidneys.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeted VEGFA therapy in regulating early acute kidney injury and late fibrosis.Acta pharmacologica Sinica · 2023Article
- Damage-mediated macrophage polarization in sterile inflammation.Frontiers in immunology · 2023Review
- Cardiac epigenetic changes in VEGF signaling genes associate with myocardial microvascular rarefaction in experimental chronic kidney disease.American journal of physiology. Heart and circulatory physiology · 2023Article
- Cardiac micro-RNA and transcriptomic profile of a novel swine model of chronic kidney disease and left ventricular diastolic dysfunction.American journal of physiology. Heart and circulatory physiology · 2022Article
- Novel Drug Delivery Technologies and Targets for Renal Disease.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Novel Protein Therapeutics Created Using the Elastin-Like Polypeptide Platform.Physiology (Bethesda, Md.) · 2021Article
- Intrarenal modulation of NF-κB activity attenuates cardiac injury in a swine model of CKD: a renal-cardio axis.American journal of physiology. Renal physiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic renovascular disease (RVD) can lead to a progressive loss of renal function, and current treatments are inefficient. We designed a fusion of vascular endothelial growth factor (VEGF) conjugated to an elastin-like polypeptide (ELP) carrier protein with an N-terminal kidney-targeting peptide (KTP). We tested the hypothesis that KTP-ELP-VEGF therapy will effectively recover renal function with an improved targeting profile. Further, we aimed to elucidate potential mechanisms driving renal recovery.
methodsUnilateral RVD was induced in 14 pigs. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified by multidetector CT imaging. Pigs then received a single intrarenal injection of KTP-ELP-VEGF or vehicle. CT quantification of renal hemodynamics was repeated 4 weeks later, and then pigs were euthanized. Ex vivo renal microvascular (MV) density and media-to-lumen ratio, macrophage infiltration, and fibrosis were quantified. In parallel, THP-1 human monocytes were differentiated into naïve macrophages (M0) or inflammatory macrophages (M1) and incubated with VEGF, KTP-ELP, KTP-ELP-VEGF, or control media. The mRNA expression of macrophage polarization and angiogenic markers was quantified (qPCR).
resultsIntrarenal KTP-ELP-VEGF improved RBF, GFR, and MV density and attenuated MV media-to-lumen ratio and renal fibrosis compared to placebo, accompanied by augmented renal M2 macrophages. In vitro, exposure to VEGF/KTP-ELP-VEGF shifted M0 macrophages to a proangiogenic M2 phenotype while M1s were nonresponsive to VEGF treatment.
conclusionsOur results support the efficacy of a new renal-specific biologic construct in recovering renal function and suggest that VEGF may directly influence macrophage phenotype as a possible mechanism to improve MV integrity and function in the stenotic kidney.
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