Background: Angiogenic gene therapy has been demonstrated to enhance perfusion to ischemic tissues, but it is unknown whether the administration of angiogenic growth factors will increase blood flow to nonischemic tissues. This study investigates whether enhanced myocardial perfusion can be mediated by adenovirus-mediated transfer of vascular endothelial growth factor 121 cDNA to nonischemic myocardium.
Methods: New Zealand White rabbits received adenovirus (5 x 10(10) particle units) encoding for vascular endothelial growth factor 121 (n = 14) or a control vector without a transgene (n = 13) or saline solution (n = 9) via direct myocardial injection. Fluorescent microsphere perfusion studies and histologic analyses were performed 4 weeks later. In a parallel study, exercise treadmill testing was performed to assess the functional effects of this therapy in Sprague-Dawley rats.
Results: Microsphere assessment of myocardial perfusion in rabbits 4 weeks after adenovirus-encoding vascular endothelial growth factor administration was greater than that for rats injected with control vector without a transgene or saline solution (3.2 +/- 0.5 vs 2.7 +/- 0.7 and 2.4 +/- 0.4, respectively; P <.03). The endothelial cell count per high power field was increased in animals injected with adenovirus-encoding vascular endothelial growth factor versus animals injected with control vector without a transgene or saline solution (147 +/- 27 vs 123 +/- 14 and 125 +/- 16 cells, respectively), although this did not reach statistical significance (P =.12). Rats treated with adenovirus-encoding vascular endothelial growth factor also demonstrated prolonged exercise tolerance compared with rats injected with control vector without a transgene or saline solution (exhaustion time: 26 +/- 5 minutes vs 19 +/- 2 minutes and 20 +/- 3 minutes, respectively; P =.006).
Conclusions: Adenovirus encoding-mediated transfer of vascular endothelial growth factor 121 induces an enhancement in regional perfusion in nonischemic myocardium that corresponds to changes in exercise tolerance. Adenovirus-encoding vascular endothelial growth factor therapy may be useful for inducing angiogenesis in the nonischemic state, such as for prophylactic therapy of early coronary artery disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jtcvs.2003.06.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Annual epidemics of influenza result in 3-5 million cases of severe illness and more than 600 000 deaths. Severe forms of influenza are usually characterized by vascular endothelial cells damage. Thus, influenza A viruses, including subtypes A(H1N1)pdm09, A(H3N2), as well as highly pathogenic avian influenza viruses, can infect the vascular endothelium, leading to activation and subsequent dysfunction of these cells.
View Article and Find Full Text PDFPregnancy and Postpartum Effects of Electronic Cigarettes on Maternal Health and Vascular Function in the Fourth Trimester.
Cardiovasc Toxicol
January 2025
Department of Physiology, Pharmacology and Toxicology, West Virginia University School of Medicine, Morgantown, WV, USA.
Pregnancy is a vulnerable time with significant cardiovascular changes that can lead to adverse outcomes, which can extend into the postpartum window. Exposure to emissions from electronic cigarettes (Ecig), commonly known as "vaping," has an adverse impact on cardiovascular function during pregnancy and post-natal life of offspring, but the postpartum effects on maternal health are poorly understood. We used a Sprague Dawley rat model, where pregnant dams are exposed to Ecigs between gestational day (GD)2-GD21 to examine postpartum consequences.
View Article and Find Full Text PDFExposomic Determinants of Atherosclerosis: Recent Evidence.
Curr Atheroscler Rep
January 2025
Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
Purpose Of Review: The exposome refers to the total environmental exposures a person encounters throughout life, and its relationship with human health is increasingly studied. This non-systematic review focuses on recent research investigating the effects of environmental factors-such as air pollution, noise, greenspace, neighborhood walkability, and metallic pollutants-on atherosclerosis, a major cause of cardiovascular disease.
Recent Findings: Studies show that long-term exposure to airborne particulate matter can impair endothelial function and elevate adhesion molecule levels, leading to vascular damage.
While key for pathogen immobilization, neutrophil extracellular traps (NETs) often cause severe bystander cell/tissue damage. This was hypothesized to depend on their prolonged presence in the vasculature, leading to cytotoxicity. Imaging of NETs (histones, neutrophil elastase, extracellular DNA) with intravital microscopy in blood vessels of mouse livers in a pathogen-replicative-free environment (endotoxemia) led to detection of NET proteins attached to the endothelium for months despite the early disappearance of extracellular DNA.
View Article and Find Full Text PDFImplications of Raftlin in different diseases: from molecular biology to diagnostic value.
Biomark Med
January 2025
Department of Clinical Laboratory, Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China.
Raftlin (raft-linking) protein is an essential component of the lipid raft structure and plays a crucial role in B and T cell signaling pathways. It facilitates B cell receptor (BCR) signaling by promoting calcium mobilization and tyrosine phosphorylation in the cells while colocalizing with BCR on the cell membrane. Interestingly, Raftlin is internalized in lipopolysaccharide-stimulated T cells by colocalization with Toll-like receptor 4 (TLR4), wherein it exerts a similar role as in B cells.
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!