The Renin-Angiotensin System: Alamandine is reduced in patients with Idiopathic Pulmonary Fibrosis
Article Sidebar
Main Article Content
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive disease without treatment that leads to death. Therefore, to control its progression to pulmonary hypertension is still a challenge. Moreover, there is no study that has investigated the Renin-Angiotensin System in patients with IPF.
Objective: Verify the plasma concentrations of Angiotensin I, Angiotensin II (AngII), Angiotensin-(1-7) [Ang- (1-7)] and Alamandine in patients with IPF.
Methods: Ten IPF patients, with or without PH, were included, and ten controls matched by sex and age. Quantitative plasma peptide concentrations (PPC) were expressed as mean and standard deviation or median and interquartile range. The Student Newman-Keuls t test was used for parametric data, Mann-Whitney for nonparametric data and, to compare proportions, the Fisher exact test was performed. The associations between clinical variables and the PPC were evaluated by Pearson or Spearman correlation coefficients. A p ≤ 0.05 was considered statistically significant.
Results: The Alamandine plasma concentration was significantly (365%) lower in the IPF group and positively associated (r = 0.876) with pulmonary artery pressure (PAP). In addition, only in control group, the forced expiratory volume (FEV1%) was positively associated (p = 0.758) with Ang-(1-7).
Conclusion: This study showed, for the first time, that there is a decrease in Alamandine participation in patients with IPF. The ACE-AngII-AT1 axis may be more active in this disease. In addition, our results suggest that Alamandine might be compensating the increase in PAP, as well as the Ang-(1-7) is improving the forced expiratory volume.
Article Details
Copyright (c) 2019 Sipriani TS, et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Navaratnam V, Fleming KM, West J, Smith CJ, Jenkins RG, et al. The rising incidence of idiopathic pulmonary fibrosis in the U.K. Thorax. 2011; 66: 462-467. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21525528 DOI: https://doi.org/10.1136/thx.2010.148031
Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006; 174: 810-816. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16809633 DOI: https://doi.org/10.1164/rccm.200602-163OC
Selman M, King TE, Pardo A; American Thoracic Society; European Respiratory Society, et al. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 2001; 134: 136-151. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11177318 DOI: https://doi.org/10.7326/0003-4819-134-2-200101160-00015
Yan Z, Kui Z, Ping Z. Reviews and prospectives of signaling pathway analysis in idiopathic pulmonary fibrosis. Autoimmun Rev. 2014; 13: 1020-1025. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25182202 DOI: https://doi.org/10.1016/j.autrev.2014.08.028
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011; 183: 788-824. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21471066
Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2006; 129: 746-752. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16537877 DOI: https://doi.org/10.1378/chest.129.3.746
Woodcock HV, Maher TM. The treatment of idiopathic pulmonary fibrosis. F1000Prime Rep. 2014; 6: 16. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24669297 DOI: https://doi.org/10.12703/P6-16
Li X, Molina-Molina M, Abdul-Hafez A, Uhal V, Xaubet A, et al. Angiotensin converting enzyme-2 is protective but downregulated in human and experimental lung fibrosis. Am J Physiol Lung Cell Mol Physiol. 2008; 295: L178-185. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18441099 DOI: https://doi.org/10.1152/ajplung.00009.2008
Molteni A, Wolfe LF, Ward WF, Ts'ao CH, Molteni LB, et al. Effect of an angiotensin II receptor blocker and two angiotensin converting enzyme inhibitors on transforming growth factor-beta (TGF-beta) and alpha-actomyosin (alpha SMA), important mediators of radiation-induced pneumopathy and lung fibrosis. Curr Pharm Des. 2007; 13: 1307-1316. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17506716 DOI: https://doi.org/10.2174/138161207780618777
Uhal BD, Kim JK, Li X, Molina-Molina M. Angiotensin-TGF-beta 1 crosstalk in human idiopathic pulmonary fibrosis: autocrine mechanisms in myofibroblasts and macrophages. Curr Pharm Des. 2007; 13: 1247-1256. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17504233 DOI: https://doi.org/10.2174/138161207780618885
Uhal BD, Li X, Piasecki CC, Molina-Molina M. Angiotensin signalling in pulmonary fibrosis. Int J Biochem Cell Biol. 2012; 44: 465-468. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22155301 DOI: https://doi.org/10.1016/j.biocel.2011.11.019
Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev. 2000; 52: 11-34. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10699153 DOI: https://doi.org/10.1016/S0031-6997(24)01434-0
Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007; 292: C82-97. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16870827 DOI: https://doi.org/10.1152/ajpcell.00287.2006
Ferrario CM, Chappell MC, Tallant EA, Brosnihan KB, Diz DI. Counterregulatory actions of angiotensin-(1-7). Hypertension. 1997; 30: 535541. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9322978 DOI: https://doi.org/10.1161/01.HYP.30.3.535
Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003; 100: 8258-8263. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12829792 DOI: https://doi.org/10.1073/pnas.1432869100
Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol. 2005; 289: H1560-1566. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15951342 DOI: https://doi.org/10.1152/ajpheart.00941.2004
Shenoy V, Ferreira AJ, Qi Y, Fraga-Silva RA, Díez-Freire C, et al. The angiotensin-converting enzyme 2/angiogenesis-(17)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med. 2010; 182: 1065-1072. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20581171 DOI: https://doi.org/10.1164/rccm.200912-1840OC
Uhal BD, Li X, Xue A, Gao X, Abdul-Hafez A. Regulation of alveolar epithelial cell survival by the ACE-2/angiotensin 1-7/Mas axis. Am J Physiol Lung Cell Mol Physiol. 2011; 301: L269-274. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21665960 DOI: https://doi.org/10.1152/ajplung.00222.2010
Lautner RQ, Villela DC, Fraga-Silva RA, Silva N, Verano-Braga T, et al. Discovery and characterization of alamandine: a novel component of the renin-angiotensin system. Circ Res. 2013; 112: 1104-1111. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23446738 DOI: https://doi.org/10.1161/CIRCRESAHA.113.301077
Mendoza-Torres E, Oyarzún A, Mondaca-Ruff D, Azocar A, Castro PF, et al. ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension. Ther Adv Cardiovasc Dis. 2015; 9: 217-237. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26275770 DOI: https://doi.org/10.1177/1753944715597623
ATS statement: guidelines for the sixminute walk test. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002; 166: 111-117. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12091180 DOI: https://doi.org/10.1164/ajrccm.166.1.at1102
Alakhras M, Decker PA, Nadrous HF, Collazo-Clavell M, Ryu JH. Body mass index and mortality in patients with idiopathic pulmonary fibrosis. Chest. 2007; 131: 1448-1453. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17400656 DOI: https://doi.org/10.1378/chest.06-2784
Bunn HF, Poyton RO. Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev. 1996; 76: 839-885. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8757790 DOI: https://doi.org/10.1152/physrev.1996.76.3.839
Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2006; 173: 475-482. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16126935 DOI: https://doi.org/10.1164/rccm.200505-840OE
Stark LJ, Powers SW. Behavioral aspects of nutrition in children with cystic fibrosis. Curr Opin Pulm Med. 2005; 11: 539-542. https://www.ncbi.nlm.nih.gov/pubmed/16217182 DOI: https://doi.org/10.1097/01.mcp.0000183051.18611.e4
Hsieh MJ, Yang TM, Tsai YH. Nutritional supplementation in patients with chronic obstructive pulmonary disease. J Formos Med Assoc. 2016; 115: 595-601. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26822811 DOI: https://doi.org/10.1016/j.jfma.2015.10.008
Königshoff M, Wilhelm A, Jahn A, Sedding D, Amarie OV, et al. The angiotensin II receptor 2 is expressed and mediates angiotensin II signaling in lung fibrosis. Am J Respir Cell Mol Biol. 2007; 37: 640-650. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17630322 DOI: https://doi.org/10.1165/rcmb.2006-0379TR
Li X, Molina-Molina M, Abdul-Hafez A, Ramirez J, Serrano-Mollar A, et al. Extravascular sources of lung angiotensin peptide synthesis in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2006; 291: L887-895. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16844946 DOI: https://doi.org/10.1152/ajplung.00432.2005
Li X, Rayford H, Uhal BD. Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice. Am J Pathol. 2003; 163: 2523-2530. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/14633624 DOI: https://doi.org/10.1016/S0002-9440(10)63607-3
Meng Y, Meng Y, Li X, Cai SX, Tong WC, et al. [Perindopril and losartan attenuate bleomycin A5-induced pulmonary fibrosis in rats]. Nan Fang Yi Ke Da Xue Xue Bao. 2008; 28: 919-924. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18583228
Mohammadi-Karakani A1, Ghazi-Khansari M, Sotoudeh M. Lisinopril ameliorates paraquat-induced lung fibrosis. Clin Chim Acta. 2006; 367: 170-174. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16458281 DOI: https://doi.org/10.1016/j.cca.2005.12.012
Wang R, Ibarra-Sunga O, Verlinski L, Pick R, Uhal BD. Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol. 2000; 279: L143-151. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10893213 DOI: https://doi.org/10.1152/ajplung.2000.279.1.L143
Jiang T, Tan L, Gao Q, Lu H, Zhu XC, et al. Plasma angiotensin-(1-7) is a potential biomarker for Alzheimer's disease. Curr Neurovasc Res. 2016. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26907614 DOI: https://doi.org/10.2174/1567202613666160224124739
Etelvino GM, Peluso AA, Santos RA. New components of the reninangiotensin system: alamandine and the MAS-related G protein-coupled receptor D. Curr Hypertens Rep. 2014; 16: 433. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24760442 DOI: https://doi.org/10.1007/s11906-014-0433-0
Grobe JL, Mecca AP, Lingis M, Shenoy V, Bolton TA, et al. Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7). Am J Physiol Heart Circ Physiol. 2007; 292: H736-742. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17098828 DOI: https://doi.org/10.1152/ajpheart.00937.2006