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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 3; pp. H1209 - H1217
• Main Authors: Kobs, Ryan W, Muvarak, Nidal E, Eickhoff, Jens C, Chesler, Naomi C
• Format: Journal Article
• Language: English
• Published: United States 01.03.2005
• Subjects: Animals; Collagen - metabolism; Elasticity; Elastin - metabolism; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Hypoxia - complications; Hypoxia - pathology; Hypoxia - physiopathology; Male; Mice; Mice, Inbred C57BL; Pulmonary Artery - pathology; Pulmonary Artery - physiology; Stress, Mechanical
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01129.2003

Departments of 1 Biomedical Engineering and 2 Biostatistics 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 Address for reprint requests and other correspondence: N. C. Chesler, Dept. of Biomedical Engineering, Univ. of Wisconsin-Madison, Rm. 2146, Engineering Centers Bldg., 1550 Engineering Dr., Madison, WI 53706-1609 (E-mail: chesler{at}engr.wisc.edu )