24 Since atherosclerosis develops over a long timescale of decades, statins can be unfavorable for long-term treatment, due to the adverse effects. 24 However, statins’ impacts are systemic throughout the body and statin use has been associated with muscle and liver damage, type 2 diabetes, and neurological side effects.
Statin therapy, for example, is a relatively successful treatment measure against timely diagnosed cardiovascular disease. 18 These diseases remain prevalent despite significant treatment advances and efforts to mitigate their progression, for a number of reasons. This suggests that GCX dysfunction, which coincides with atherosclerosis, can indeed be targeted for enhanced drug delivery, offering a new approach in cardiovascular disease therapy.Ĭardiovascular diseases, such as those derived from atherosclerotic vessel hardening due to cholesterol-and macrophage-filled plaque formation, are the leading causes of death worldwide. GCX degradation in the ligated LCA correlated to increased GNS infiltration of the ligated LCA wall. 10-nm gold nanospheres (GNS) coated with polyethylene glycol (PEG) were delivered intravenously. After ligation, the LCA vessel wall exhibited a loss of continuity of the GCX layer on the intima. In mice, the left carotid artery (LCA) was partially ligated to disturb blood flow, which induces GCX degradation, endothelial dysfunction, and atherosclerosis. The present study assessed if the cell culture findings translate to selective nanoparticle uptake in animal vessels. In prior cell culture studies, GCX degradation significantly increased endothelial cell uptake of nanoparticle vehicles that are designed for drug delivery, compared to the effects of intact GCX. This initiates pro-atherosclerotic lipids and inflammatory cells to penetrate vessel walls, and at the same time this can be leveraged for targeted drug delivery. Endothelial glycocalyx (GCX) degradation compromises endothelial barrier function and increases vascular permeability. Therapies for atherosclerotic cardiovascular disease should target early disease stages and specific vascular sites where disease occurs.
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