Atherosclerosis is the primary cause of hardening and narrowing arteries, leading to cardiovascular disease accounting for the high mortality in the United States. For developing effective treatments for atherosclerosis, considerable efforts have been devoted to developing in vitro models. Compared to animal models, in vitro models can provide great opportunities to obtain data more efficiently, economically. Therefore, this review discusses the recent progress in in vitro models for atherosclerosis studies, including traditional two-dimensional (2D) systems cultured on the tissue culture plate, 2D cell sheets, and recently emerged microfluidic chip models with 2D culture. In addition, advanced in vitro three-dimensional models such as spheroids, cell-laden hydrogel constructs, tissue-engineered blood vessels, and vessel-on-a-chip will also be covered. Moreover, the functions of these models are also summarized along with model discussion. Lastly, the future perspectives of this field are discussed.
Atherosclerosis is a major contributor to many cardiovascular events, including myocardial infarction, ischemic stroke, and peripheral arterial disease, making it the leading cause of death worldwide. High-density lipoproteins (HDL), also known as "good cholesterol", have been shown to demonstrate anti-atherosclerotic efficacy through the removal of cholesterol from foam cells in atherosclerotic plaques. Because of the excellent anti-atherosclerotic properties of HDL, in the past several years, there has been tremendous attention in designing HDL mimicking nanoparticles (NPs) of varying functions to image, target, and treat atherosclerosis. In this review, we are summarizing the recent progress in the development of HDL mimicking NPs and their applications for atherosclerosis.
Blood clots (90%) originate from the left atrial appendage (LAA) in non-valvular atrial fibrillation patients and are a major cause of embolic stroke. Long-term anticoagulation therapy has been used to prevent thrombus formation, but its use is limited in patients at a high risk for bleeding complications. Thus, left atrial appendage closure (LAAC) devices for LAA occlusion are well-established as an alternative to the anticoagulation therapy. However, the anticoagulation therapy is still required for at least 45 days post-implantation to bridge the time until complete LAA occlusion by neoendocardium coverage of the device. In this study, we applied an endothelium-mimicking nanomatrix to the LAAC device membrane for delivery of nitric oxide (NO) to enhance endothelialization, with the goal of possibly being able to reduce the duration of the anticoagulation therapy. The nanomatrix was uniformly coated on the LAAC device membranes and provided sustained release of NO for up to 1 month in vitro. In addition, the nanomatrix coating promoted endothelial cell proliferation and reduced platelet adhesion compared to the uncoated device membranes in vitro. The nanomatrix-coated and uncoated LAAC devices were then deployed in a canine LAA model for 22 days as a pilot study. All LAAC devices were not completely covered by neoendocardium 22 days post-implantation. However, histology image analysis showed that the nanomatrix-coated LAAC device had thicker neoendocardium coverage compared to the uncoated device. Therefore, our in vitro and in vivo results indicate that the nanomatrix coating has the potential to enhance endothelialization on the LAAC device membrane, which could improve patient outcomes by shortening the need for extended anticoagulation treatment.
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