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Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue. PLoS One 2015;10(8):e0134601 PMID: 26244896 PMCID: PMC4526652

Abstract

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

Author List

Santos CF, Morandini AC, DionĂ­sio TJ, Faria FA, Lima MC, Figueiredo CM, Colombini-Ishikiriama BL, Sipert CR, Maciel RP, Akashi AP, Souza GP, Garlet GP, Rodini CO, Amaral SL, Becari C, Salgado MC, Oliveira EB, Matus I, Didier DN, Greene AS

Author

Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Amino Acid Sequence
Angiotensin I
Angiotensin II
Animals
Cells, Cultured
Female
Gingiva
Humans
Inflammation
Male
Middle Aged
Peptide Fragments
Periodontitis
Periodontium
Rats, Wistar
Receptors, Angiotensin
Renin
Renin-Angiotensin System



View this publication's entry at the Pubmed website PMID: 26244896
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