Statins Enhance Rotator Cuff Healing by Stimulating the COX2/PGE2/EP4 Pathway

Abstract

Although chronic inflammation contributes to the development of tendinopathy, study results advocate for a positive role of PGE2 in tendon healing during the acute inflammatory phase that follows tendon surgical repair. It is therefore suggested that ATV should be further investigated as a possible modality to improve tendon healing.

Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells

“…In the present study, we find that all six statins are able to decrease PGE2 at lower concentrations; however, at the maximal concentration (100  μ M), PGE2 release was either unaffected or elevated beyond LPS induction alone. Statin-induced increases in PGE2 production have been reported in nonneurological models, although these have been in models of acute in vivo inflammation via experimental rotator cuff injury [69]. Again, further investigation may be warranted to clarify whether the observations from the present study are due to dose-dependent effects.…”

Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern

“…A previous in vitro study has shown that the cells appear to arrest in the G1-phase of the cell cycle when treated with simvastatin, an effect that could be reversed by mevalonate or two down-stream intermediates [18]. There are however also studies which show no effect on proliferation by treatment with lovastatin [17] or even a higher proliferation with atorvastatin treatment [13]. The discrepancy between these results could perhaps be a question of timing or dosage.…”

“…However, statin treatment during tendon or ligament healing appears to have a positive effect [13–15], especially on tendon to bone healing [13, 15]. Statins have been suggested to destabilize cell membranes, lead to tenocyte apoptosis or disturb matrix remodeling through an altered expression and activity of MMPs and collagens [8, 16].…”

“…Statins have been suggested to destabilize cell membranes, lead to tenocyte apoptosis or disturb matrix remodeling through an altered expression and activity of MMPs and collagens [8, 16]. Statins can also influence cell migration [13, 17, 18] and cell proliferation by arresting the cells in the G1-phase [18]. However the results on cell proliferation are again contradictive.…”

Pediatric Statin Administration: Navigating a Frontier with Limited Data

“…For example, patients with sickle cell disease can develop oxidative stress and chronic inflammation to their distal vasculature as a result of transient vaso-occlusion and subsequent [196][197][198] Decrease decline in GFR Prevent contrast induced acute kidney injury Decrease risk of stroke Fracture injuries, bone healing, & osteoporosis [199][200][201][202][203][204] Promote mesenchymal cell differentiation to osteoblasts Protect osteoblasts from apoptosis Reduce osteoclast activity and bone resorption HIV [205][206][207][208][209][210][211] Slow progression of vascular disease on ART Improve flow-mediated vasodilation Implement immunomodulation Reduce all-cause mortality Immunomodulation [212][213][214] Inhibit interferon production Decrease T cell activation Infection [215][216][217][218] Reduce risk of mortality from bacterial and viral infection Lupus [219][220][221][222] Reduce C-reactive protein Reduce circulating chemokines Improve endothelial function Polycystic ovary syndrome [223][224][225] Reduce markers of inflammation Reduce androgenic steroid concentrations Rheumatoid arthritis [226][227][228][229][230][231] Reduce risk of mortality Reduce joint pain/swelling Reduce markers of inflammation Rotator cuff injury 232,233 Stimulate migration and adhesi...…”