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Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue.

Santos CF, Morandini AC, Dionísio 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 - PLoS ONE (2015)

Bottom Line: However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts.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.Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic Representation of the Renin-Angiotensin System.Angiotensin-I converting enzyme, ACE; angiotensin I converting enzyme 2, ACE-2; angiotensin II 1 receptor, AT1R; angiotensin II 2 receptor, AT2R; aminopeptidase, AP; aminopeptidase A, APA; aminopeptidase N, APN; carboxypeptidase, CPP; endopeptidase, EP; Mas receptor, MasR; Mas-related gene type D receptor, MrgDR; neprilysin, NEP; (pre)prorenin receptor, PRR.
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pone.0134601.g001: Schematic Representation of the Renin-Angiotensin System.Angiotensin-I converting enzyme, ACE; angiotensin I converting enzyme 2, ACE-2; angiotensin II 1 receptor, AT1R; angiotensin II 2 receptor, AT2R; aminopeptidase, AP; aminopeptidase A, APA; aminopeptidase N, APN; carboxypeptidase, CPP; endopeptidase, EP; Mas receptor, MasR; Mas-related gene type D receptor, MrgDR; neprilysin, NEP; (pre)prorenin receptor, PRR.

Mentions: The renin-angiotensin system (RAS) regulates or modulates numerous physiological functions including blood pressure, electrolyte balance, inflammation and the release of various peptide hormones. In particular, peptides such as vasopressin and angiotensinogen (AGT) are released and transported through the circulatory system as part of the extended RAS modulating inflammation, oxidative stress, fibrosis and cell proliferation. Fig 1 depicts a broad schematic pathway of the RAS. Briefly, prorenin is converted to renin; this rate-limited step releases renin into the circulatory system thereby cleaving AGT forming angiotensin I (1–10) (Ang I). Ang I can be cleaved by angiotensin I-converting enzyme (ACE) to form angiotensin II (1–8) (Ang II) or by angiotensin I-converting enzyme 2 (ACE-2) to form angiotensin 1–9 (Ang 1–9). ACE-2 also catalyses the cleavage of Ang II to form angiotensin 1–7 (Ang 1–7). ACE can also cut Ang 1–9 to form Ang 1–7, and alamandine can be formed by Ang 1–7. Additionally, Ang II can form angiotensin III (2–8), angiotensin A and angioprotectin.


Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue.

Santos CF, Morandini AC, Dionísio 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 - PLoS ONE (2015)

Schematic Representation of the Renin-Angiotensin System.Angiotensin-I converting enzyme, ACE; angiotensin I converting enzyme 2, ACE-2; angiotensin II 1 receptor, AT1R; angiotensin II 2 receptor, AT2R; aminopeptidase, AP; aminopeptidase A, APA; aminopeptidase N, APN; carboxypeptidase, CPP; endopeptidase, EP; Mas receptor, MasR; Mas-related gene type D receptor, MrgDR; neprilysin, NEP; (pre)prorenin receptor, PRR.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526652&req=5

pone.0134601.g001: Schematic Representation of the Renin-Angiotensin System.Angiotensin-I converting enzyme, ACE; angiotensin I converting enzyme 2, ACE-2; angiotensin II 1 receptor, AT1R; angiotensin II 2 receptor, AT2R; aminopeptidase, AP; aminopeptidase A, APA; aminopeptidase N, APN; carboxypeptidase, CPP; endopeptidase, EP; Mas receptor, MasR; Mas-related gene type D receptor, MrgDR; neprilysin, NEP; (pre)prorenin receptor, PRR.
Mentions: The renin-angiotensin system (RAS) regulates or modulates numerous physiological functions including blood pressure, electrolyte balance, inflammation and the release of various peptide hormones. In particular, peptides such as vasopressin and angiotensinogen (AGT) are released and transported through the circulatory system as part of the extended RAS modulating inflammation, oxidative stress, fibrosis and cell proliferation. Fig 1 depicts a broad schematic pathway of the RAS. Briefly, prorenin is converted to renin; this rate-limited step releases renin into the circulatory system thereby cleaving AGT forming angiotensin I (1–10) (Ang I). Ang I can be cleaved by angiotensin I-converting enzyme (ACE) to form angiotensin II (1–8) (Ang II) or by angiotensin I-converting enzyme 2 (ACE-2) to form angiotensin 1–9 (Ang 1–9). ACE-2 also catalyses the cleavage of Ang II to form angiotensin 1–7 (Ang 1–7). ACE can also cut Ang 1–9 to form Ang 1–7, and alamandine can be formed by Ang 1–7. Additionally, Ang II can form angiotensin III (2–8), angiotensin A and angioprotectin.

Bottom Line: However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts.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.Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus