Abstract
Periodontitis is a local and systemic inflammatory condition and a risk factor of atherosclerosis, but no studies investigated the effect of a statin on atherogenesis affected by severe periodontitis. In this study, we investigated the effect of rosuvastatin (RSV) on atherogenesis in Apolipoprotein E-deficient mice receiving silk ligature placement around the maxillary second molars. Mice with the ligature placement developed severe periodontitis and vascular inflammation. RSV significantly inhibited the development of periodontitis and vascular inflammation and remarkably blocked the increased lipid deposition and the atherogenic gene expression in the arterial wall and aortic sinus induced by severe periodontitis. To understand the mechanistic effect of RSV on periodontitis-associated atherogenesis, we investigated the in vitro effect of RSV on various effect of TNF-α, a major proinflammatory cytokine for periodontitis and atherogenesis. We found that RSV notably inhibited the TNF-α-induced osteoclast formation, endothelial cell phenotypic changes, foam cell formation, and the expression of CD47 and other oncogenes in arterial smooth muscle cells. Taken together, our study indicates that RSV prevents the exacerbation of atherosclerosis induced periodontitis by inhibiting local, systemic and vascular inflammation, as well as the expression of CD47 from arterial smooth muscle cells in mice.
Highlights
Periodontal disease comprises a wide range of local inflammatory conditions that affect the supporting structures of the teeth including gingiva, bone and periodontal ligament[1]
To understand the mechanistic effect of RSV on periodontitis and periodontitis-associated atherosclerosis, we investigated the in vitro effect of RSV on the phenotype of vascular endothelial cells, macrophages, and smooth muscle cells exposed to TNF-α, a proinflammatory cytokine associated with the development of periodontitis and atherosclerosis
To determine if RSV could inhibit osteoclast differentiation, we isolated bone marrow cells from wild-type male C57BL/6 J mice and induced osteoclast differentiation ex vivo. This was achieved by culturing the cells in the presence of mouse macrophage-colony stimulating factor (M-CSF) for 3 days, followed by exposing the cells to receptor activator of nuclear factor kappa-Β ligand (RANKL) and M-CSF for 0–3 days with or without RSV
Summary
Periodontal disease comprises a wide range of local inflammatory conditions that affect the supporting structures of the teeth including gingiva, bone and periodontal ligament[1]. Hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, reduce low density lipoprotein-cholesterol (LDL-C) levels and effectively reduce the risk of atherosclerotic cardiovascular disease (CVD)[7]. In addition to their LDL-C lowering effects, statins increase high density lipoprotein-cholesterol (HDL-C), decrease triglycerides (TG), and promote anti-inflammatory activities and pleiotropic positive effects in various systems, including the cardiovascular, immune, and skeletal systems[8,9]. Our study shows that RSV remarkably limits atherosclerosis induced by severe periodontitis in mice by suppressing the development of aberrant phenotype of endothelial cells, macrophages, and smooth muscle cells
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