AI Article Synopsis
- The study explores alternative treatments for critical limb ischemia (CLI), focusing on the role of vascular growth factors like VEGF and FGF-2 in the disease's progression.
- Skin and muscle biopsies were taken from CLI patients and controls to measure levels of these growth factors and their locations.
- Results indicated that CLI patients had lower VEGF levels in distal skin but higher levels in calf muscle compared to control samples, while FGF-2 levels showed similar patterns, suggesting a complex relationship between these growth factors and CLI.
Article Abstract
Background: For patients with critical limb ischemia (CLI), there is a great need for alternative treatment strategies. One option is therapeutic angiogenesis by administration of vascular growth factors. The lack of convincing clinical data supporting this strategy may be due to the ignorance of endogenous angiogenic processes in CLI. To evaluate the importance of vascular growth factors in the pathogenesis in CLI and provide information for clinical growth factor treatment trials, we determined the levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in the ischemic legs of patients with this disease.
Methods: Skin and muscle biopsies from the calf and groin were gathered from 25 patients with CLI. Control samples came from 10 orthopedic patients and from 5 patients who were undergoing coronary artery bypass. The concentration of VEGF and FGF-2 in the biopsies was measured by enzyme-linked immunoassay, and to localize growth factor production, biopsied sections were immunostained.
Results: Patients with CLI had lower levels of VEGF in distal skin samples than in proximal ones (mean difference: 16.7 pg/mg total protein, 95% confidence interval: -1.0 to -32.3, P =.038), but these levels were similar to those in distal samples from control subjects (8.0, -4.6 to 20.5, P =.65). In muscle, VEGF concentrations were similar in calf and groin (5.4, -12.4 to 23.1, P =.55), but distal levels were higher than in distal samples from control subjects (23.7, 1.2 to 56.7, P =.028). Skin FGF levels tended to be higher in distal samples (45.3, 26.5 to 117.5, P =.090) and were higher than in skin from control subjects (106.2, -11.4 to 223.8, P =.050). Also in muscle, distal samples had higher levels of FGF-2 (35.6, -1.6 to 59.7, P =.006), but these levels were similar to what was found in control subjects (29.4., -16.3 to 81.2, P =.39). Growth factors were located in connective tissue between muscle fibers. In skin, the predominant FGF-2 staining was just below the epidermal layer, whereas VEGF appeared in the dermal layer.
Conclusions: The results indicate that there are elevated concentrations of FGF-2 in calf muscle, whereas VEGF concentrations do not appear to be higher in the ischemic part of the leg in patients with CLI. These findings suggest that VEGF supplementation may be a more appropriate strategy for therapeutic angiogenesis to the calf area for CLI than FGF-2.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jvs.2003.07.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modular DNA origami-based electrochemical detection of DNA and proteins.
Proc Natl Acad Sci U S A
January 2025
Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125.
The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte.
View Article and Find Full Text PDFinfection accelerates postnatal maturation of the intestinal epithelium.
Proc Natl Acad Sci U S A
January 2025
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen 52074, Germany.
Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.
View Article and Find Full Text PDFDeep conservation complemented by novelty and innovation in the insect eye ground plan.
Proc Natl Acad Sci U S A
January 2025
Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
A spectacular diversity of forms and features allow species to thrive in different environments, yet some structures remain relatively unchanged. Insect compound eyes are easily recognizable despite dramatic differences in visual abilities across species. It is unknown whether distant insect species use similar or different mechanisms to pattern their eyes or what types of genetic changes produce diversity of form and function.
View Article and Find Full Text PDFComputational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFANAC044 orchestrates mitochondrial stress signaling to trigger iron-induced stem cell death in root meristems.
Proc Natl Acad Sci U S A
January 2025
Ministry of Education Key Laboratory of Environment Remediation and Ecological Health, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
While iron (Fe) is essential for life and plays important roles for almost all growth related processes, it can trigger cell death in both animals and plants. However, the underlying mechanisms for Fe-induced cell death in plants remain largely unknown. S-nitrosoglutathione reductase (GSNOR) has previously been reported to regulate nitric oxide homeostasis to prevent Fe-induced cell death within root meristems.
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!