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Publication : The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension.

First Author  Ooi CY Year  2010
Journal  Am J Physiol Heart Circ Physiol Volume  299
Issue  6 Pages  H1823-31
PubMed ID  20852040 Mgi Jnum  J:164655
Mgi Id  MGI:4834934 Doi  10.1152/ajpheart.00493.2009
Citation  Ooi CY, et al. (2010) The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 299(6):H1823-31
abstractText  Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1(R/R)). These mice and littermate controls that have normal collagen degradation (Col1a1(+/+)) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia.
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