hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice

Author:

Chen Wei1ORCID,Kim Sharon1,Lee Alicia1,Kim Yun-Jeong1ORCID,Chang Chungyu2ORCID,Ton-That Hung2ORCID,Kim Reuben13,Kim Sangjae4ORCID,Park No-Hee135ORCID

Affiliation:

1. The Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, 714 Tiverton Ave., Los Angeles, CA 90095, USA

2. Section of Oral Biology, UCLA School of Dentistry, 714 Tiverton Avenue, Los Angeles, CA 90095, USA

3. UCLA Jonsson Comprehensive Cancer Center, 10833 Le Conte Ave., Los Angeles, CA 90095, USA

4. Teloid Inc., 920 Westholme Avenue, Los Angeles, CA 90024, USA

5. Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., Los Angeles, CA 90095, USA

Abstract

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer’s disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

Funder

UCLA Chancellor’s Office and various private donations

Publisher

MDPI AG

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