HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/H1209    most recent 01129.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Kobs, R. W. Articles by Chesler, N. C. Search for Related Content PubMed PubMed Citation Articles by Kobs, R. W. Articles by Chesler, N. C.

Linked mechanical and biological aspects of remodeling in mouse pulmonary arteries with hypoxia-induced hypertension

Departments of ¹Biomedical Engineering and ²Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin

Submitted 1 December 2003 ; accepted in final form 22 October 2004

Right heart failure due to pulmonary hypertension causes significant morbidity and mortality. To study the linked vascular mechanical and biological changes that are induced by pulmonary hypertension, we mechanically tested isolated left main pulmonary arteries from mice exposed to chronic hypobaric hypoxia and performed histological assays on contralateral vessels. In isolated vessel tests, hypoxic vessels stretched less in response to pressure than controls at all pressure levels. Given the short length and large diameter of the pulmonary artery, the tangent Young's modulus could not be measured; instead, an effective elastic modulus was calculated that increased significantly with hypoxia [(280 kPa (SD 53) and 296 kPa (SD 50) for 10 and 15 days, respectively, vs. 222 kPa (SD 35) for control; P < 0.02)]. Hypoxic vessels also had higher damping coefficients [(0.063 (SD 0.017) and 0.054 (SD 0.014) for 10 and 15 days, respectively, vs. 0.033 (SD 0.016) for control; P < 0.002)], indicating increased energy dissipation. The increased stiffness with hypoxia correlated with an increase in collagen thickness (percent collagen multiplied by wall thickness) as well as the sum of elastin and collagen thicknesses measured histologically in the artery wall. These results highlight the mechanobiological changes in the pulmonary vasculature that occur in response to hypoxia-induced pulmonary hypertension. Furthermore, they demonstrate significant vascular mechanical and biological changes that would increase pulmonary vascular impedance, leading to right heart failure.

pulmonary hypertension; elastic modulus; damping; elastin; collagen

This article has been cited by other articles:

				S. R. Lammers, P. H. Kao, H. J. Qi, K. Hunter, C. Lanning, J. Albietz, S. Hofmeister, R. Mecham, K. R. Stenmark, and R. Shandas Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1451 - H1459. [Abstract] [Full Text] [PDF]

				M. Rabinovitch, N. Chesler, and R. C. Molthen Point:Counterpoint: Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature J Appl Physiol, October 1, 2007; 103(4): 1449 - 1451. [Full Text] [PDF]

				K. R. Stenmark, K. A. Fagan, and M. G. Frid Hypoxia-Induced Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms Circ. Res., September 29, 2006; 99(7): 675 - 691. [Abstract] [Full Text] [PDF]

				Y.-F. Chen, J.-A. Feng, P. Li, D. Xing, Y. Zhang, R. Serra, N. Ambalavanan, E. Majid-Hassan, and S. Oparil Dominant negative mutation of the TGF-beta receptor blocks hypoxia-induced pulmonary vascular remodeling J Appl Physiol, February 1, 2006; 100(2): 564 - 571. [Abstract] [Full Text] [PDF]