Abstract
Elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD) and is partially regulated by Matrix Gla Protein (MGP), via a vitamin K-dependent pathway. The aim was to assess vitamin K status in COPD as well as associations between vitamin K status, elastin degradation, lung function parameters and mortality. A total of 192 COPD patients and 186 age-matched controls were included. In addition to this, 290 COPD patients from a second independent longitudinal cohort were also included. Vitamin K status was assessed by measuring plasma inactive MGP levels and rates of elastin degradation by measuring plasma desmosine levels. Reduced vitamin K status was found in COPD patients compared to smoking controls (p < 0.0005) and controls who had never smoked (p = 0.001). Vitamin K status was inversely associated with desmosine (cohort 1: p = 0.001; cohort 2: p = 0.004). Only few significant associations between vitamin K status and lung function parameters were found. Mortality was higher in COPD patients within the quartile with the lowest vitamin K status compared to those within the other quartiles (hazard ratio 1.85, 95% confidence interval (CI), 1.21–2.83, p = 0.005). In conclusion, we demonstrated reduced vitamin K status in COPD and an inverse association between vitamin K status and elastin degradation rate. Our results therefore suggest a potential role of vitamin K in COPD pathogenesis.
Highlights
Chronic obstructive pulmonary disease (COPD) is defined by a combination of chronic respiratory symptoms and persistent airflow limitation, caused by small airways disease, parenchymal destruction or a combination of both [1]
Dp-ucMGP was significantly higher in COPD patients (1127 pmol/L, 95% confidence intervals (CI), 996 to 1274 pmol/L) compared to smoking controls (821 pmol/L, 95% CI, 716 to 939 pmol/L, p < 0.0005) and controls who had never smoked (841 pmol/L, 95% CI, 709 to 997 pmol/L, p = 0.001, Figure 2)
After exclusion of VKA users (n = 17) and subjects in which VKA use was unknown (n = 6), dp-ucMGP remained significantly higher in COPD patients (650 pmol/L, 95% CI, 601 to 703 pmol/L) compared to smoking controls (472 pmol/L, 95% CI, 433 to 513 pmol/L, p < 0.0005) and controls who had never smoked (484 pmol/L, 95% CI, 424 to 552 pmol/L, p = 0.001); and no statistical difference was found between smoking controls and controls who had never smoked (p = 0.726)
Summary
Chronic obstructive pulmonary disease (COPD) is defined by a combination of chronic respiratory symptoms and persistent airflow limitation, caused by small airways disease, parenchymal destruction (emphysema) or a combination of both [1]. Smoking is indisputably the most important risk factor for this disease in the Western world [1], it is still unclear why some smokers develop COPD whereas others with comparable smoking history do not. 2g01e9 vidence suggests that the fat-soluble vitamins A and D are imp loifc1a5ted in the pathogeneGseisneotifcCvaOriPanDce[o2f–fe4r]s.oVnliytalimttleinexKplaanlsaotiobne, alonnd gthserteofotrheeenfavitr-osnomluenbtlael fvaicttaorms bineyso; nhdoswmeovkienrg, its role in COPD has—ntehveeerxpboeseonme—xpslhoorueldd.beVaidtadmresinsedK. Is important for the activation of clotting factors in the liver but is an eAsscecunmtiuallactionfgaecvtoidrenincethsuegagcestitsvathtaiot nthoeffavta-sroilouublseovtihtaemripnsroAteainnds D[5]a.reMimatprliicxatGedlainPrthoetein (MGP) is a vitamipCnaOtKhPo-DdgeehnpaesesninsedovefernCbtOepPeDnroe[t2xe–pi4lno].raVendit.daVmoiitnnameKionaflKstohibseeilfmoenpwgosrpttaoonttthefenofrtattih-nseohaliucbbtiilvteoavtriisotanomfoifnecslla;ohstottiiwnngecvfaearcl,ctoiitrfisscrioanlteithoinen [6], since other anti-lcivaelcr ibfuytinisgalpsoroanteeisnsesn, tsiaulcchofaacstofreitnutihne, aacrteivtaotioonlaorfgveartioouesnottheerrtphreotienintse[r5i]o.rMoaftrtixheGlealParsottieninfibres [6,7]. Arterial ca(lMciGfiPca) tisioanvsitsatmairnt Kin-deelpaesntdinenfit bprroetsei[n8a]nadnodnecaonf thbeefienwdpuoctendt inhribaittsortshorfoeulagshtinthcaelcaifdicmationnistration of vitamin K [a6n],tsaingcoenoitshtesr a(VntKi-cAalsc)ifybiyngpprreovteeinnst,insugchMasGfPetuaicnt,iavrae ttiooonla[r9g]e.toTehnetemr tihneeirnatelriizoartoiof tnheoeflaesltainstin results in enhancefaiddbmrepisnr[io6stt,7rea]o.tilAoynrttiecroifaellvaciastlatcmiinfiicndateiKognrsaansdttaaargttoiionnnise,tlsagsit(viVneKfnAibstr)ehsab[ty8]paprnordetveceaansnteinbgesyinnMdtGuhcPeesdiasicntiivnraacttrsioetnahrso[e9us]g.phTathhreeallel to the calcium comntineenrtaloizfaetiloanstoifnefilabsrtiensr[e1s0u]lt.sAinneannhiamncaedl mproodteeollyotficeelalassttoincadlecgirnaodsaitisohn,agsivsuenggtheasttepdrottehaaset MGP has protecstyivnethpesrios pinecrrteiaessesagparianlsletl etloastthien cdaelcgiurmadcaotniotennt[9o]f. The rate odlfueenmlgaostnitssistnruaetd.edTeghfaervarodautaeratoiboflenelpairssotipanecrdctieeegslreoardfaaMtteiGodnPi[ins6]aCacrcOeelnPeorDattoeandnlyidnapCrpeOlliPacDatebldaenttdoorbmelolaootderdtvaetlosistmeylso,[r1bta3ult]it.aylTs[o1h3te]o.refore, we hypothesizTehderethfoaret,vwiteamhyipnotKhepsilzaeydstahartovleitaimniCn OKPpDlaypsatahroogleeninesCisOPthDropuatghhogMenGesPis mthoroduughlatMioGnP(Figure 1)
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