Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome

Abstract

Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-␤). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-␤ signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (Mg⌬). Six-week-old male heterozygous Mg⌬ and wild-type mice were challenged with Porphyromonas gingivalis, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (CT), and inflammatory cytokine levels were examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption in both Mg⌬ and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-␣) levels were significantly higher in infected Mg⌬ mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected Mg⌬ mice. Telmisartan also significantly decreased levels of TGF-␤, IL-17, and TNF-␣ in infected Mg⌬ mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.

Effect of telmisartan on levels of IL‐1, TNF‐α, down‐regulated COX‐2, MMP‐2, MMP‐9 and RANKL/RANK in an experimental periodontitis model

“…In a study by Suda et al. () that investigated the effect of TELM on the progression of periodontitis in a mouse model of Marfan syndrome, the authors concluded that treatment with TELM significantly suppressed alveolar bone resorption and decreased the levels of TGF‐β, IL‐17 and TNF‐α.…”

Controversies and evolving new mechanisms in subarachnoid hemorrhage

“…In addition, genome-wide association studies are helpful to identify novel genetic factors that contribute to intracranial aneurysm susceptibility. Consequently, it is possible to produce an aneurysm on cerebral vessels experimentally using genetic technology (Suda et al, 2013). Furthermore, ensuring reproducibility of results, the efficacy of a treatment option should be confirmed in multiple species and in multiple laboratories before beginning translation to a clinical study (Tajiri et al, 2013).…”

Simvastatin modulates gingival cytokine and MMP production in a rat model of ligature-induced periodontitis

“…On the other hand, the recent knowledge on the inflammatory pathways involved in this disease has unleashed novel venues for therapy, with increased attention to strategies that modulate the inflammatory response 7. Recently, an anti-inflammatory effect was suggested for antihypertensive drugs (angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, β-blockers) in periodontitis 8,9. More recently, the cholesterol-lowering drug simvastatin, used as adjuvant in hypertensive patients with dyslipidemia, was suggested to have a protective effect against experimental10,11 and human periodontitis 9,12.…”