The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with nonviable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 +/- 10.8 versus 31.0 +/- 5.8%, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 +/- 11.9 versus 36.8 +/- 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.
Intimal hyperplasia is the leading cause of long-term failure in coronary artery bypass vein grafting, coronary artery stenting, angioplasty, arteriovenous fistula for dialysis, and allograft transplantation. Intimal hyperplasia is a product of vascular smooth muscle cell proliferation, migration through the internal elastic lamina, and deposition of extracellular matrix proteins driven by growth factors in the vasculature. This vascular pathology results in a progressive diminution of the vessel lumen and serves as a site for thrombosis and atherosclerotic lesions. A key cell type in the initiation of intimal hyperplasia is the vascular endothelial cell, which appears to have down-stream effects on the vascular smooth muscle proliferation and migration. Currently, the only means available for prevention of intimal hyperplasia is through inhibition of mammalian target of rapamycin (mTOR) with the immunosuppressant rapamycin. mTOR integrates up-stream signals from growth factors such as IL-2 and senses the cellular nutrient and energy levels and redox status. This presentation will discuss the potential means of preserving the vascular endothelial cell and, thereby, reducing the development of intimal hyperplasia in our open-heart surgical patients.
Vascular diseases such as aneurysm and aortic dissection account for almost 16,000 deaths in the United States annually. In both of these diseases vascular inflammation is a common pathogenic factor. Another common pathologic feature of vascular disease includes structural matrix remodeling. It is also increasingly believed that inflammation may play a key role in the formation and progression of atherosclerotic vascular disease. Angiotensin II (AngII), a potent vasopressor, is also a strong inducer of vascular inflammation and aortic remodeling in atherosclerosis-prone mice. Based on this knowledge studies have been conducted using subcutaneous AngII infusion in order to produce aortic remodeling and aneurysm formation, with acute thoracic and abdominal aortic dissections [1].
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.