Objective-Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). Methods and Results-Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl 2 -induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. Key Words: abdominal aortic aneurysm n angiopoietin-like protein 2 n chronic inflammation n macrophage n matrix metalloproteinase Conclusions-Macrophage-derived
oth coronary artery bypass grafting and percutaneous coronary intervention ameliorate angina pectoris, prevent myocardial infarction and improve the long-term survival of patients with atherosclerotic coronary artery disease. However, the nature of coronary arteries significantly impacts the quality of life. Standard therapies for myocardial revascularization are often limited because of diffuse lesions or small-caliber vessels. Angiogenic therapy to induce myocardial neovascularization is not dependent on vessel caliber and provides an alternative treatment alone or in combination with standard revascularization. Basic fibroblast growth factor (bFGF) is a potent angiogenic protein that induces endothelial and smooth muscle cell proliferation in vivo and elicits angiogenesis that includes the migration and proliferation of endothelial cells, vascular tube formation and linkage to the extant vascular network. 1 Intracoronary injections of bFGF reduce infarct size in a canine model of myocardial infarction and improve myocardial function in chronically ischemic porcine hearts. 2,3 We have previously shown that the intramyocardial administration of bFGF increased the number of capillaries and arterioles in the peri-infarct region, increased regional myocardial blood flow and consequently improved ven- Circulation Journal Vol.70, April 2006tricular function in a canine infarction model. 4 However, angiogenesis induced by growth factors has not been always successful. Despite high binding affinity for acidic polysaccharides such as heparin and heparan sulfate in the extracellular matrix, bFGF has a short biological half-life in tissues. 5 The sustained release of bFGF might help to enhance its angiogenic activity in vivo. 6,7 Gelatin is a nontoxic, biodegradable, natural polymer with low antigenicity and gelatin hydrogel is considered to be a preferable matrix for the sustained release of protein drugs, such as growth factors. 8,9 However, the effects of intramyocardial injections of slow-release bFGF on vascular growth, cardiomyocyte apoptosis and cardiac function have not been investigated in detail. The present study evaluates the ability of gelatin hydrogels to enhance the benefits of bFGF on neoangiogenesis, cardiomyocyte apoptosis, myocardial fibrosis, ventricular remodeling and cardiac function in a rat infarction model. Methods Preparation of bFGFHuman recombinant bFGF and gelatin hydrogels were provided by Kaken Pharmaceutical, Tokyo, Japan. Gelatin with an isoelectric point of 4.9 was prepared using alkaline treatment of bovine collagen with Ca(OH)2. To obtain gelatin hydrogels that incorporated bFGF, 0.7 ml of saline containing 350 g of bFGF was impregnated into freezedried hydrogels. The release of biologically active bFGF is sustained as a result of hydrogel degradation in vivo. Empty gelatin hydrogels free of bFGF were similarly prepared. Background Basic fibroblast growth factor (bFGF) stimulates neoangiogenesis. Incorporation into biodegradable gelatin hydrogels provides the sustained release of bFGF....
The relationships between oxygen delivery (DO2), oxygen consumption (VO2), and the extraction rate (ER = VO2/DO2 x 100) in patients undergoing cardiopulmonary bypass (CPB) may differ from the normal physiologic state due to the oxygen debt acquired during CPB. Blood gas analysis and hemodynamic parameters were repeatedly measured for the determination of DO2 and VO2 in 40 patients undergoing CPB, every 8 h during the first 48 h postoperatively. As a control, 20 patients who had suffered acute myocardial infarction (AMI) were also studied using the same protocol. In the CPB group, a regression analysis showed that VO2 was significantly dependent on DO2, even within the physiologic range of DO2 (>500 ml/min per m2); VO2 = 121.4 + 0.0844 x DO2 (r = 0.254, P = 0.023). Conversely, in the AMI group, no such supply-dependent consumption was observed within the same range of DO2. At an ER of 30%, which is the optimal value in general, the DO2 of the CPB group was 575 ml/min per m2 and that of the AMI group was 493 ml/min per m2. All these results suggest that patients undergoing CPB need a much higher oxygen supply to recover from the oxygen debt acquired during open heart surgery.
The use of cryopreserved aortic allografts in cardiovascular surgery is widespread and has resulted in excellent outcomes. However, it is controversial whether cryopreservation suppresses the antigenicity of tissue. We designed experimental models to study whether the cryopreservation process alters antigenicity in comparison with that found in fresh and glutaraldehyde treated tissues. Fresh, cryopreserved, and glutaraldehyde treated thoracic aorta from Brown Norway rats were subcutaneously implanted into Lewis rats. Inflammatory cells infiltrating around the grafts were measured on days 7, 14, 28, and 56 after implantation. The glutaraldehyde treated grafts showed significantly less infiltration than the fresh or cryopreserved grafts (p < 0.005). No significant difference was detected between the fresh and cryopreserved grafts. Another study examined the effect of modifications of the aortic allograft on subsequent allogeneic skin graft antigenicity. Subcutaneous implantation of fresh, cryopreserved, and glutaraldehyde treated aortic grafts from Brown Norway into Lewis rats resulted in subsequent skin graft rejection at 4.4+/-0.7, 5.1+/-0.8, and 6.6+/-2.1 days, respectively. There was no significant difference between the fresh and cryopreserved groups; whereas skin grafts in the glutaraldehyde group survived longer than those in the cryopreserved group. These results indicate that cryopreservation had no significant influence on antigenic suppression of arterial allografts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.