The mechanobiology of pulmonary vascular remodeling in the congenital absence of eNOS.
Primary pulmonary hypertension is a rare but deadly disease. Lungs extracted from PPH patients are deficient in endothelial nitric oxide synthase (eNOS), making the eNOS-null mouse a potentially useful model of the disease. To better understand the progression of pulmonary vascular remodeling in the congenital absence of eNOS, we induced pulmonary hypertension in eNOS-null mice using hypobaric hypoxia, and then quantified large artery structure and function in contralateral vessels. In particular, to assess structure we quantified diameter, wall thickness, and collagen, elastin and smooth muscle cell content; to quantify function we performed pressure-diameter tests. After remodeling, the pulmonary arteries had increased wall, collagen and elastin thicknesses compared to controls (P<0.05). The remodeled pulmonary arteries also had increased elastic moduli at low and high strains compared to controls (P<0.05). The increases in moduli at low and high strain correlated with increases in elastin and collagen thickness, respectively (P<0.05). These results provide insight into the mechanobiology of pulmonary vascular remodeling in the congenital absence of eNOS, and the coupled nature of these changes.
Kobs
Ryan W
RW
Department of Biomedical Engineering, University of Wisconsin - Madison, 2146 Engineering Centers Building, 1550 Engineering Drive, Madison, WI 53706-1609, USA.
Chesler
Naomi C
NC
D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004549:Elastin / Q000032:analysis / Q000378:metabolism; D005260:Female; D005629:Frozen Sections; D006651:Histocytochemistry; D000860:Hypoxia / Q000235:genetics / Q000503:physiopathology*; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology
D003094:Collagen; D004549:Elastin; D052250:Nitric Oxide Synthase Type III