Upregulation of collagen messenger RNA expression occurs immediately after lung damage.
BACKGROUND
Mortality of ARDS still exceeds 50%. Though pulmonary fibrosis is a marker of severe prognosis in the evolution of ARDS, its onset is not yet established. Cardiopulmonary bypass (CPB), usually utilized in patients with a previously normal lung, can cause ARDS and often causes alveolar damage, the earliest lesion observed in ARDS, thus providing a unique opportunity to study the molecular mechanisms of fibrogenesis.


OBJECTIVE
To measure immediately after CPB, at the onset of alveolar damage, the expression of messenger RNAs (mRNAs) for collagen type I.


METHODS
Pre-CPB and post-CPB lung biopsy specimens were obtained from patients submitted to myocardial revascularization for coronary artery disease. Alveolar damage was characterized by comparison between before and after specimens and quantified by point counting of polymorphonuclear cells (PMN). Type I collagen mRNAs were quantified by scanning densitometry of Northern blot autoradiographs, corrected for RNA loading by 18S ribosomal RNA hybridization.


RESULTS
Alveolar damage was characterized by lung interstitial edema and by polymorphonuclear cell infiltration after CPB (PMN pre-CPB 0.010+/-0.004xPMN post-CPB 0.052+/-0.022; n=7; p=0.0017, t test). Type I collagen mRNA increased 91.1+/-68.2% (Ln pre-CPBxLn post-CPB; n=15; p<0.00001, t test) immediately after CPB (mean CPB time, 108.8+/-37.2 min).


CONCLUSIONS
Fibrogenesis, as measured at the molecular level, is a very early event following diffuse alveolar damage, attributable mainly to resident fibroblast activation.
Deheinzelin
D
D
Servico de Pneumologia, Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo, Brazil.
Jatene
F B
FB
Saldiva
P H
PH
Brentani
R R
RR
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D015152:Blotting, Northern; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D003327:Coronary Disease / Q000601:surgery; D015342:DNA Probes / Q000737:chemistry; D003720:Densitometry; D004587:Electrophoresis, Agar Gel; D005260:Female; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D015415:Biomarkers; D015342:DNA Probes; D012333:RNA, Messenger; D003094:Collagen