GV1001 Inhibits the Severity of the Ligature-Induced Periodontitis and the Vascular Lipid Deposition Associated with the Periodontitis in Mice

Abstract

GV1001, a 16 amino acid peptide derived from the catalytic segment of human telomerase reverse transcriptase, was developed as an anti-cancer vaccine. Subsequently, it was found to exhibit anti-inflammatory and anti-Alzheimer’s disease properties. Periodontitis is a risk factor for a variety of systemic diseases, including atherosclerosis, a process in which chronic systemic and vascular inflammation results in the formation of plaques containing lipids, macrophages, foam cells, and tissue debris on the vascular intima. Thus, we investigated the effect of GV1001 on the severity of ligature-induced periodontitis, vascular inflammation, and arterial lipid deposition in mice. GV1001 notably reduced the severity of ligature-induced periodontitis by inhibiting gingival and systemic inflammation, alveolar bone loss, and vascular inflammation in wild-type mice. It also significantly lowered the amount of lipid deposition in the arterial wall in ApoE-deficient mice receiving ligature placement without changing the serum lipid profile. In vitro, we found that GV1001 inhibited the Receptor Activator of NF-κB ligand (RANKL)-induced osteoclast formation and tumor necrosis factor-α (TNF-α)-induced phenotypic changes in endothelial cells. In conclusion, our study suggests that GV1001 prevents the exacerbation of periodontitis and atherosclerosis associated with periodontitis partly by inhibiting local, systemic, and vascular inflammation and phenotypic changes of vascular endothelial cells.

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

“…Given that drugs targeting a single molecular objective may face challenges in demonstrating beneficial effects in AD clinical trials [ 56 , 57 ], compounds simultaneously targeting multiple processes might offer paramount solutions against AD. Numerous studies, including ours, confirm that GV1001 stands out as a compound with the ability to simultaneously affect multiple cellular targets [ 11 , 12 , 58 ]. Overall, GV1001 is proposed as a potential solution against AD due to its ability to simultaneously target multiple processes, in contrast to drugs focusing on a single molecular target.…”

“…Whole blood, gingival swab samples, gingival tissue, aortic roots, heart, brain, entire arteries, and maxillae were collected from the mice and processed or stored as described previously [ 11 ].…”

“…The fulllength of the aorta-to-iliac bifurcation was opened along the ventral midline and dissected free of the animal under a stereomicroscope. Then, the aorta was stained with Sudan IV, as previously described, and pinned out flat, intimal side up, between cover slides [11]. We captured the aortic images with a Nikon digital camera and analyzed them using ImageJ software version 1.48 (NIH, Bethesda, MD, USA; http://imagej.nih.gov/ij (accessed on 19 April 2014)).…”

“…Total RNA was extracted from mouse gingival, aortic, and brain tissues using the RNeasy micro kit (Qiagen, Inc., Hilden, Germany) and reverse transcribed as described previously [11]. In situ hybridization was performed on frozen heart sections and formalin-fixed and paraffin-embedded gingival and brain tissue sections using Alexa Fluor 488 (Thermo Fisher Scientific, Waltham, MA, USA) labeled oligonucleotide probes specific for Pg (5 ′ -CAATACTCGTATCGCCCGTTATTC-3 ′ ).…”

“…Additionally, it downregulates enolase1-produced proinflammatory cytokines [ 10 ]. In our previous study, we showed that GV1001 prevented the development of ligature-induced periodontitis and atherosclerosis [ 11 ]. Recently, it was reported that GV1001 suppressed neuroinflammation, reduced amyloid-β (Aβ) oligomer levels, and decreased phospho-Tau by activating gonadotropin-releasing hormone receptors (GnRHRs) and their downstream signaling pathways in mice [ 12 ].…”