Felodipine Allays High Cholesterol-Aggravated Periodontitis via Attenuating 27-Hydroxycholesterol

Hypercholesterolemia may exacerbate chronic periodontitis (CP) but the mechanism is uncertain. 27-Hydroxycholesterol (27HC) is metabolized from cholesterol through the action of cytochrome P450 27A1 (CYP27A1) and may participate in diseases associated with high cholesterol. This study aimed to examine the pro-inflammatory effects of 27HC, its role in hypercholesterolemia-aggravated CP, and the therapeutic action of felodipine, an inhibitor of CYP27A1.

J774 murine macrophages were used. The levels of cholesterol, 27HC, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and CC chemokine ligand 2 (CCL2) were measured. Ligature-induced periodontitis was established in male rats fed with a normal diet (ND) or a high-fat/high-cholesterol diet (HFHCD). Disease progression was evaluated by micro-computed tomography, histology, and immunohistochemistry.

Cholesterol enhanced the production of 27HC in macrophages, which promoted the expressions of iNOS, COX-2 and CCL2. HFHCD rats had hypercholesterolemia, higher serum and gingival 27HC, and more advanced periodontitis compared to ND rats. Felodipine suppressed cholesterol-induced 27HC production in macrophages. Felodipine treatment did not affect serum cholesterol but significantly decreased serum and gingival 27HC and alleviated ligature-induced periodontitis.

Our data support the importance of 27HC in mediating hypercholesterolemia-aggravated periodontitis. Inhibiting 27HC production may have therapeutic value in periodontitis or other inflammatory diseases exacerbated by high cholesterol.