“…Whereas some neointima formation is necessary for vessel healing after stenting, to bury the stent struts within the vessel wall and to prevent exposure to the flowing blood, excessive neointima formation narrows the lumen. 6 The endothelium plays a central role in maintaining vascular health by virtue of the endothelial cells' (ECs) antiinflammatory and anticoagulant properties. 7 It has been demonstrated that in a rat model of carotid artery dilation by percutaneous transluminal coronary angioplasty (PTCA) balloon catheter, the first step in allowing VSMC proliferation from the tunica media to the intima is the occurrence of internal elastic lamina (IEL) rupture (Figure 2).…”
“…Whereas some neointima formation is necessary for vessel healing after stenting, to bury the stent struts within the vessel wall and to prevent exposure to the flowing blood, excessive neointima formation narrows the lumen. 6 The endothelium plays a central role in maintaining vascular health by virtue of the endothelial cells' (ECs) antiinflammatory and anticoagulant properties. 7 It has been demonstrated that in a rat model of carotid artery dilation by percutaneous transluminal coronary angioplasty (PTCA) balloon catheter, the first step in allowing VSMC proliferation from the tunica media to the intima is the occurrence of internal elastic lamina (IEL) rupture (Figure 2).…”
“…Whereas some neointima formation is necessary for vessel healing after stenting in order to imbed the stent within the vessel wall and to prevent exposure to blood flow, excessive neointima formation narrows the lumen 44 . In both rats (this paper) and humans 45 , de-differentiation of medial VSMCs occurs within 2-4 days after surgery.…”
Coronary artery disease represents the leading cause of mortality in the developed world. Percutaneous coronary intervention (PCI) involving stent placement remains disadvantaged by restenosis or thrombosis. Vascular gene-therapy-based methods may be approached, but lack a vascular gene delivery vector.
We report a safe and efficient long-term transduction of rat carotid vessels after balloon-injury intervention with a translational optimized AAV2.5 vector. Compared to other known AAV serotypes, AAV2.5 demonstrated the highest transduction efficiency of human coronary artery vascular smooth muscle cells (VSMC) in vitro. Local delivery of AAV2.5-driven transgenes in injured carotid arteries resulted in transduction as soon as day 2 after surgery and persisted for at least 30 days. In contrast to adenovirus 5 vector, inflammation was not detected in AAV2.5-transduced vessels. The functional effects of AAV2.5-mediated gene transfer on neointimal thickening were assessed using the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) human gene, known to inhibit VSMC proliferation. At 30 days, human SERCA2a mRNA was detected in transduced arteries. Morphometric analysis revealed a significant decrease of neointimal hyperplasia in AAV2.5-SERCA2a transduced arteries: 28.36±11.30 (n=8) vs 77.96±24.60 (n=10) μm2, in AAV2.5-GFP-infected, p<0.05.
In conclusion, AAV2.5 vector can be considered as a promising safe and effective vector for vascular gene therapy.
“…Histological studies revealed that the web and membrane examined 5 h after stenting were composed of fibrin, whereas those examined 1 month later were composed of collagen fibers (Fig. 8) [18]. Fig.…”
Novel imaging techniques using biomarkers have clarified the mechanisms of hitherto unanswered or misunderstood phenomena of coronary artery disease and enabled evaluation of myocardial blood and tissue fluid flows in vivo. Dye-staining coronary angioscopy using Evans blue (EB) as the biomarker can visualize fibrin and damaged endothelial cells, revealing that the so-called platelet thrombus is frequently a fibrin-rich thrombus; occlusive transparent fibrin thrombus, but not platelet thrombus, is not infrequently a cause of acute coronary syndrome; “fluffy” coronary luminal surface is caused by fibrin threads arising from damaged endothelial cells and is a residue of an occlusive thrombus after autolysis in patients with acute coronary syndrome without angiographically demonstrable coronary stenosis; and web or membrane-like fibrin thrombus is a cause of stent edge restenosis. Fluorescent angioscopy using visual or near-infrared light wavelengths is now used clinically for molecular imaging of the substances such as lipoproteins and cholesterol that constitute coronary plaques. Dye-staining cardioscopy using EB or fluorescein enables direct and real-time visualization of subendocardial microcirculation.
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