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Felodipine Allays High Cholesterol-Aggravated Periodontitis via Attenuating 27-Hydroxycholesterol
Hung-Ying Lin1, Sze-Kwan Lin1,2, Cheng-Ning Yang2
1Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
Oral Diseases
|November 5, 2025
Summary
High cholesterol worsens gum disease by increasing 27-hydroxycholesterol (27HC). Felodipine, by inhibiting 27HC production, shows therapeutic potential for periodontitis and other inflammatory conditions linked to high cholesterol.
Area of Science:
- Biochemistry
- Immunology
- Periodontology
Background:
- Hypercholesterolemia is linked to chronic periodontitis (CP), but the underlying mechanisms remain unclear.
- 27-hydroxycholesterol (27HC), a metabolite of cholesterol, may play a role in cholesterol-associated diseases.
- Cytochrome P450 27A1 (CYP27A1) is involved in 27HC metabolism.
Purpose of the Study:
- To investigate the pro-inflammatory effects of 27HC.
- To determine 27HC's role in hypercholesterolemia-aggravated CP.
- To evaluate the therapeutic potential of felodipine, a CYP27A1 inhibitor, in this context.
Main Methods:
- Murine macrophages were used to assess cholesterol, 27HC, iNOS, COX-2, and CCL2 levels.
- Ligature-induced periodontitis was established in rats fed normal or high-fat/high-cholesterol diets.
- Disease progression was assessed using micro-CT, histology, and immunohistochemistry.
Main Results:
- Cholesterol increased 27HC production in macrophages, upregulating iNOS, COX-2, and CCL2.
- Rats on a high-fat/high-cholesterol diet exhibited hypercholesterolemia, elevated 27HC, and more severe periodontitis.
- Felodipine reduced 27HC production and alleviated periodontitis in rats, without altering serum cholesterol levels.
Conclusions:
- 27HC is crucial in mediating CP exacerbation by hypercholesterolemia.
- Inhibiting 27HC production presents a potential therapeutic strategy for periodontitis and other inflammatory conditions associated with high cholesterol.
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