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Objective: To investigate the effects of vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ASODN) on the mRNA and protein expression of VEGF, Flt-1, and kinase insert domain containing receptor (KDR) and VEGF excretion in human gallbladder carcinoma cells.
Methods: Human gallbladder carcinoma cells of the line GBC-SD were cultured and transfected with VEGF ASODN and sense oligodeoxynucleotide (SODN) mediated by Oligofectamine. The toxicity of SODN and Oligofectamine to the GBC-SD cells was examined by MTT method. RT-PCR was used to detect the mRNA and expression of VEGF, Flt-1, and KDR, and ELISA was used to detect the protein expression of VEGF.
Results: MTT method showed that SODN and Oligofectamine were not toxic to the GBC-SD cells. The mRNA expression levels of VEGF, Flt-1, and KDR of the ASODN and ASODN + Oligofectamine groups were all significantly lower than those of the control group (all P < 0.05), and were the lowest 72 hours after transfection, and then gradually increased. ELISA showed that there were not significant differences in the VEGF protein concentration in the supernatant of the GBC-SD cells among the SODN, SODN + Oligofectamine, and control groups (all P < 0.05), however, the VEGF protein concentration in the supernatant of the GBC-SD cells of the ASDN and ASDN + Oligofectamine groups were significantly lower than that of the control group (both P < 0.05).
Conclusion: VEGF ASODN inhibits the mRNA and protein expression of VEGF, Flt-1, and KDR and VEGF excretion in human gallbladder carcinoma cells. Oligofectamine strengthens the effect of ASODN.
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J Mol Histol
September 2025
Department of Gynecology and Obstetrics, Yantaishan Hospital, Yantai, 264001, Shandong, China.
Pre-eclampsia (PE) is a common pregnancy complication, closely associated with endothelial dysfunction and inhibition of angiogenesis. This study aims to explore the pathological mechanisms causing endothelial dysfunction and suppressed angiogenesis in PE, with the aim of identifying potential drug targets. Human umbilical vein endothelial cells (HUVECs) were exposed to angiotensin II (Ang-II) to mimic PE-related endothelial dysfunction.
View Article and Find Full Text PDFBiomolecules
July 2025
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.
Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin's potential as a therapeutic agent, functioning not only to control blood sugar levels but also to enhance vascular health and strengthen cardiac resilience in diabetes.
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August 2025
Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Vascular endothelial growth factor receptor 1 (VEGFR1) is a key regulator of endothelial function, angiogenesis, inflammation, and cardiomyocyte survival, with both beneficial and deleterious effects in cardiovascular disease. In this review, we provide some key information on the molecular biology governing VEGFR1 function, its role in cardiovascular diseases and describe gene therapy strategies targeting either membrane-bound or its soluble isoform sFLT1 to treat these diseases. Clinical Relevance Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide.
View Article and Find Full Text PDFPLoS Comput Biol
August 2025
Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Constitutively secreted by endothelial cells, soluble FLT1 (sFLT1 or sVEGFR1) binds and sequesters extracellular vascular endothelial growth factors (VEGF), thereby reducing VEGF binding to VEGF receptor tyrosine kinases and their downstream signaling. In doing so, sFLT1 plays an important role in vascular development and in the patterning of new blood vessels in angiogenesis. Here, we develop multiple mechanistic models of sFLT1 secretion and identify a minimal mechanistic model that recapitulates key qualitative and quantitative features of temporal experimental datasets of sFLT1 secretion from multiple studies.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
August 2025
Eye Institute and Affiliated Xiamen Eye Center, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Medicine, Xiamen University, Xiamen, Fujian, People's Republic of China.
Purpose: Retinal neovascular diseases, often associated with elevated vascular endothelial growth factor (VEGF) levels, are major causes of blindness. Current therapies lack sustained efficacy and safety. This study aimed to evaluate the effectiveness of an adeno-associated virus 2 (AAV2)-based gene therapy vector carrying soluble fms-like tyrosine kinase-1 (sFLT-1) and short hairpin RNA targeting VEGF (shVEGF) in treating retinal neovascularization.
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