Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma.
The walls of pulmonary capillaries are extremely thin, and wall stress increases greatly when capillary pressure rises. Alveolar hypoxia causes pulmonary vasoconstriction and hypertension, and if this is uneven, some capillaries may be exposed to high transmural pressure and develop stress failure. There is evidence that increased wall stress causes capillary remodeling. In this study we exposed Madison strain Sprague-Dawley rats to normobaric hypoxia (10% oxygen) for 6 h or 3 d (short-term group), and for 3 d or 10 d (long-term group). Peripheral lung tissue was then collected and messenger RNA (mRNA) levels were determined for extracellular matrix (ECM) proteins and growth factors. Collagen content (hydroxyproline) was also measured. Levels of mRNA for alpha2(IV) procollagen increased sixfold after 6 h of hypoxia and sevenfold after 3 d of hypoxia, and then decreased after 10 d exposure. Levels of mRNA for platelet-derived growth factor-B (PDGF-B) doubled after 6 h of hypoxia but returned to control values after 3 d. mRNA levels for alpha1(I) and alpha1(III) procollagens and fibronectin were increased after 3 d of hypoxia (by seven- to 12-fold, 1.6- to eightfold, and 12-fold, respectively), then decreased toward control values after 10 d. In contrast, neither levels of mRNA for vascular endothelial growth factor (VEGF) nor collagen content changed. These results suggest that alveolar hypoxia causes vascular remodeling in lung parenchyma, and are consistent with capillary wall remodeling in response to increased wall stress.
Berg
J T
JT
Department of Medicine, University of California San Diego, La Jolla, California, USA.
Breen
E C
EC
Fu
Z
Z
Mathieu-Costello
O
O
West
J B
JB
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005353:Fibronectins / Q000235:genetics; D005786:Gene Expression Regulation; D006909:Hydroxyproline / Q000235:genetics; D006976:Hypertension, Pulmonary / Q000209:etiology; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011347:Procollagen / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D015996:Survival Rate; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014661:Vasoconstriction / Q000502:physiology
D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D006909:Hydroxyproline