Alamandine attenuates arterial remodelling induced by transverse aortic constriction in mice

Carregando...
Imagem de Miniatura
Citações na Scopus
25
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
PORTLAND PRESS LTD
Autores
SOUZA-NETO, Fernando Pedro de
SILVA, Mario de Morais e
SANTUCHI, Melissa de Carvalho
ALCANTARA-LEONIDIO, Thais Cristina de
MOTTA-SANTOS, Daisy
OLIVEIRA, Aline Cristina
MELO, Marcos Barrouin
CANTA, Giovanni Naves
Citação
CLINICAL SCIENCE, v.133, n.5, p.629-643, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Aims: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine (Ala(1)-angiotensin-(1-7)) is a new biologically active peptide from the RAS, interacting withMas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated events. In the present study, we investigated the effects of alamandine on ascending aorta remodelling after transverse aortic constriction (TAC) in mice. Methods and results: C57BL/6J male mice were divided into the following groups: Sham (sham-operated), TAC (operated) and TAC+ALA (operated and treated with alamandine-HP beta CD (2-Hydroxypropyl-beta-cyclodextrin), 30 mu g/kg/day, by gavage). Oral administration of alamandine for 14 days attenuated arterial remodelling by decreasing ascending aorta media layer thickness and the cells density in the adventitia induced by TAC. Alamandine administration attenuated ascending aorta fibrosis induced by TAC, through a reduction in the following parameters; total collagen deposition, expression collagen III and transforming growth factor-beta (TGF-beta) transcripts, matrix metalloproteinases (MMPs) activity and vascular expression of MMP-2. Importantly, alamandine decreased vascular expression of proinflammatory genes as CCL2, tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), and was able to increase expression of MRC1 and FIZZ1, pro-resolution markers, after TAC surgery. Conclusion: Alamandine treatment attenuates vascular remodelling after TAC, at least in part, through anti-fibrotic and anti-inflammatory effects. Hence, this work opens new avenues for the use of this heptapeptide also as a therapeutic target for vascular disease.
Palavras-chave
Referências
  1. Bertagnolli M, 2014, PEPTIDES, V51, P65, DOI 10.1016/j.peptides.2013.11.006
  2. Brooke BS, 2008, NEW ENGL J MED, V358, P2787, DOI 10.1056/NEJMoa0706585
  3. Santana ABC, 2014, BIOMED RES INT, DOI 10.1155/2014/914102
  4. Chen J, 2011, CLIN EXP PHARMACOL P, V38, P570, DOI 10.1111/j.1440-1681.2011.05544.x
  5. Da Silva AR, 2017, EUR J CLIN INVEST, V47, P117, DOI 10.1111/eci.12708
  6. deAlmeida Angela C, 2010, J Vis Exp, DOI 10.3791/1729
  7. Du XJ, 2011, CLIN EXP PHARMACOL P, V38, P559, DOI 10.1111/j.1440-1681.2011.05558.x
  8. Faugeroux J, 2013, HYPERTENSION, V62, P203, DOI 10.1161/HYPERTENSIONAHA.111.00974
  9. Fraga-Silva RA, 2015, VASC PHARMACOL, V74, P103, DOI 10.1016/j.vph.2015.08.014
  10. Frederiks WM, 2004, J HISTOCHEM CYTOCHEM, V52, P711, DOI 10.1369/jhc.4R6251.2004
  11. Habiyakare B, 2014, INT J EXP PATHOL, V95, P290, DOI 10.1111/iep.12087
  12. Hekmat AS, 2017, CIRC J, V81, P405, DOI 10.1253/circj.CJ-16-0958
  13. Hrenak J, 2016, INT J MOL SCI, V17, DOI 10.3390/ijms17071098
  14. Humphrey JD, 2015, CIRC RES, V116, P1448, DOI 10.1161/CIRCRESAHA.114.304936
  15. Irani K, 2001, CIRC RES, V88, P858, DOI 10.1161/hh0901.091205
  16. Kuang SQ, 2013, ARTERIOSCL THROM VAS, V33, P2172, DOI 10.1161/ATVBAHA.113.301624
  17. Lautner RQ, 2013, CIRC RES, V112, P1104, DOI 10.1161/CIRCRESAHA.113.301077
  18. Li JZ, 2013, CARDIOL CLIN, V31, P493, DOI [10.1016/j.ccl.2013.07.011, 10.1016/j.cc1.2013.07.011]
  19. Li P, 2018, LIFE SCI, V206, P106, DOI 10.1016/j.lfs.2018.04.010
  20. Liu C, 2018, AMINO ACIDS, V50, P1071, DOI 10.1007/s00726-018-2583-x
  21. Liu DG, 2016, ARTERIOSCL THROM VAS, V36, P442, DOI 10.1161/ATVBAHA.115.306861
  22. Liu Y, 2016, EUR J PHARMACOL, V791, P535, DOI 10.1016/j.ejphar.2016.07.008
  23. Lu H, 2012, CLIN SCI, V123, P531, DOI 10.1042/CS20120097
  24. Magalhaes GS, 2015, BRIT J PHARMACOL, V172, P2330, DOI 10.1111/bph.13057
  25. Marques FD, 2011, HYPERTENSION, V57, P477, DOI 10.1161/HYPERTENSIONAHA.110.167346
  26. Mathur D, 2016, SCI REP-UK, V6, DOI 10.1038/srep36617
  27. Milewicz DM, 2008, ANNU REV GENOM HUM G, V9, P283, DOI 10.1146/annurev.genom.8.080706.092303
  28. Moltzer E, 2011, PHARMACOL THERAPEUT, V131, P50, DOI 10.1016/j.pharmthera.2011.04.002
  29. Motta-Santos D, 2016, HYPERTENS RES, V39, P506, DOI 10.1038/hr.2016.28
  30. Pacurari M, 2014, INT J INFLAMM, DOI 10.1155/2014/689360
  31. Page-McCaw A, 2007, NAT REV MOL CELL BIO, V8, P221, DOI 10.1038/nrm2125
  32. Qaradakhi T, 2017, CARDIOVASC THER, V35, DOI 10.1111/1755-5922.12306
  33. Qaradakhi T, 2016, PHARMACOL RES, V111, P820, DOI 10.1016/j.phrs.2016.07.025
  34. ROCKMAN HA, 1991, P NATL ACAD SCI USA, V88, P8277, DOI 10.1073/pnas.88.18.8277
  35. Santuchi MD, 2019, MEDIAT INFLAMM, DOI 10.1155/2019/2401081
  36. Sellers SL, 2018, AM J PATHOL, V188, P574, DOI 10.1016/j.ajpath.2017.11.006
  37. Songstad NT, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0089559
  38. Uchiyama T, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0178769
  39. Wang XX, 2016, J MOL CELL CARDIOL, V97, P180, DOI 10.1016/j.yjmcc.2016.05.012
  40. Wei H, 2012, P NATL ACAD SCI USA, V109, pE841, DOI 10.1073/pnas.1202081109
  41. Xu R, 2016, PEPTIDES, V86, P85, DOI 10.1016/j.peptides.2016.10.005