Objective: Endothelial outgrowth cells (EOC) decrease inflammation and improve endothelial repair. Inflammation aggravates kidney injury in renal artery stenosis (RAS), and may account for its persistence upon revascularization. We hypothesized that EOC would decrease inflammatory (M1) macrophages and improve renal recovery in RAS.
Approach And Results: Pigs with 10 weeks of RAS were studied 4 weeks after percutaneous transluminal renal angioplasty (PTRA+stenting) or sham, with or without adjunct intrarenal delivery of autologous EOC (10×10(6)), and compared with similarly treated normal controls (n=7 each). Single-kidney function, microvascular and tissue remodeling, inflammation, oxidative stress, and fibrosis were evaluated. Four weeks after PTRA, EOC were engrafted in injected RAS-kidneys. Stenotic-kidney glomerular filtration rate was restored in RAS+EOC, RAS+PTRA, and RAS+PTRA+EOC pigs, whereas stenotic-kidney blood flow and angiogenesis were improved and fibrosis attenuated only in EOC-treated pigs. Furthermore, EOC increased cell proliferation and decreased the ratio of M1 (inflammatory)/M2 (reparative) macrophages, as well as circulating levels and stenotic-kidney release of inflammatory cytokines. Cultured-EOC released microvesicles in vitro and induced phenotypic switch (M1-to-M2) in cultured monocytes, which was inhibited by vascular endothelial growth factor blockade. Finally, a single intrarenal injection of rh-vascular endothelial growth factor (0.05 μg/kg) in 7 additional RAS pigs also restored M1/M2 ratio 4 weeks later.
Conclusions: Intrarenal infusion of EOC after PTRA induced a vascular endothelial growth factor-mediated attenuation in macrophages inflammatory phenotype, preserved microvascular architecture and function, and decreased inflammation and fibrosis in the stenotic kidney, suggesting a novel mechanism and therapeutic potential for adjunctive EOC delivery in experimental RAS to improve PTRA outcomes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644980 | PMC |
| http://dx.doi.org/10.1161/ATVBAHA.113.301164 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Global trends and hotspots of type 2 diabetes in children and adolescents: A bibliometric study and visualization analysis.
World J Diabetes
January 2025
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Background: Epidemiological surveys indicate an increasing incidence of type 2 diabetes mellitus (T2DM) among children and adolescents worldwide. Due to rapid disease progression, severe long-term cardiorenal complications, a lack of effective treatment strategies, and substantial socioeconomic burdens, it has become an urgent public health issue that requires management and resolution. Adolescent T2DM differs from adult T2DM.
View Article and Find Full Text PDFHUVECs-derived exosomes increase neovascularization and decrease limb necrosis in hindlimb ischemia.
Narra J
December 2024
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral arterial disease (PAD) and imposes a significantly high burden due to its high risk of mortality and amputation. Revascularization is the first-line treatment for CLTI; however, the amputation rate remains high, and approximately one-third of patients are not eligible for this treatment. Therefore, there is an urgent need for more effective therapeutic strategies.
View Article and Find Full Text PDFEarly activation of macrophage-2 with IL-4 in stromal vascular fraction increases VEGF levels and adipocyte count and maintains volume of fat graft in Wistar rats ().
Narra J
December 2024
Department of Radiology, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia.
Several previous studies have demonstrated the benefits of early macrophage 2 activation fat grafts supplemented with macrophage culture. However, this approach is considered impractical in clinical settings because of intraperitoneal induction use. The aim of this study was to investigate the effect of early stromal vascular fraction (SVF) macrophage-2 activation with IL-4 on fat graft survival compared to SVF alone using an animal model for better fat graft viability.
View Article and Find Full Text PDFSecretome from hypoxic mesenchymal stem cells as a potential therapy for ischemic stroke: Investigations on and expression.
Narra J
December 2024
Faculty of Medicine, Universitas HKBP Nommensen, Medan, Indonesia.
Ischemic stroke is a sudden onset of neurological deficit resulting from a blockage in cerebral blood vessels, which can lead to brain tissue damage, chronic disability, and increased risk of mortality. Secretome from hypoxic mesenchymal stem cells (SH-MSC) is a potential therapy to improve neurological deficit by increasing the expression of vascular endothelial growth factor (VEGF) and reducing glial fibrillary acidic protein (GFAP). These effects can reduce the infarction area of ischemic stroke.
View Article and Find Full Text PDFAerobic exercise improves spatial memory in a rat model of meningitis.
Narra J
December 2024
Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret Surakarta, Indonesia.
Infections of the nervous system, such as acute bacterial meningitis, pose serious health problems that require immediate intervention. In experimental animals, exposure to lipopolysaccharide (LPS) is used to induce meningitis. Aside from drug intervention to reduce inflammation in meningitis, aerobic exercise helps to maintain the regulatory mechanisms of brain homeostasis through anti-inflammatory mechanisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!