ArticleHypertension (Dallas, Tex. : 1979)2019
Targeted VEGF (Vascular Endothelial Growth Factor) Therapy Induces Long-Term Renal Recovery in Chronic Kidney Disease via Macrophage Polarization.
Article in Hypertension (Dallas, Tex. : 1979), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 52 citations in OpenAlex.
- Renal single-nucleus transcriptomic of a new model of cardiovascular-kidney-metabolic syndrome in aging swine.American journal of physiology. Renal physiology · 2026Article
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- Association Between Chronic Kidney Disease and Subclinical Hypothyroidism Categorized by Hypertension Status.Diseases (Basel, Switzerland) · 2026Article
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- 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
- A New Model of Chronic Kidney Disease, Metabolic Derangements, and Heart Failure with Preserved Ejection Fraction in Aging Swine.American journal of nephrology · 2025Article
- Molecular mechanisms and therapeutic advances of peritubular capillary neogenesis in acute kidney injury.Frontiers in molecular biosciences · 2025Review
- Glycolysis in Peritubular Endothelial Cells and Microvascular Rarefaction in CKD.Journal of the American Society of Nephrology : JASN · 2025Article
- The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair.Journal of nanobiotechnology · 2023Review
- Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization: State-of-the-art in bone and associated tissue regeneration.Bioactive materials · 2023Review
- Secreted Cytokines within the Urine of AKI Patients Modulate TP53 and SIRT1 Levels in a Human Podocyte Cell Model.International journal of molecular sciences · 2023Article
- Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023Review
- Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury.Frontiers in physiology · 2023Article
- Targeting immunometabolism during cardiorenal injury: roles of conventional and alternative macrophage metabolic fuels.Frontiers in physiology · 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
- Pro- and anti-fibrotic effects of vascular endothelial growth factor in chronic kidney diseases.Renal failure · 2022Review
- De novo SIX2 activation in human kidneys treated with neonatal kidney stem/progenitor cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Mechanosensitive Ion Channel PIEZO1 Signaling in the Hall-Marks of Cancer: Structure and Functions.Cancers · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation. CKD was induced in 14 pigs, which were observed for 14 weeks. At 6 weeks, renal blood flow and filtration were quantified using multidetector computed tomography, and then pigs received single intrarenal ELP-VEGF or placebo (n=7 each). Renal function was quantified again 4 and 8 weeks later. Pigs were euthanized and renal microvascular density, angiogenic and inflammatory markers, fibrosis, macrophage infiltration, and phenotype were quantified. Loss of renal hemodynamics in CKD was progressively recovered by ELP-VEGF therapy, accompanied by improved renal microvascular density, fibrosis, and expression of inflammatory mediators. Although renal macrophage infiltration was similar in both CKD groups, ELP-VEGF therapy distinctly shifted their phenotype from proinflammatory M1 to VEGF-expressing M2. Our study unravels potential mechanisms and feasibility of a new strategy to offset progression of CKD using drug-delivery technologies. The results indicate that renal recovery after ELP-VEGF therapy was largely driven by modulation of renal macrophages toward VEGF-expressing M2 phenotype, restoring VEGF signaling and sustaining improvement of renal function and microvascular integrity in CKD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.