title: Effects of collagen deposition on passive and active mechanical properties of large pulmonary arteries in hypoxic pulmonary hypertension.
abstract: Proximal pulmonary artery (PA) stiffening is a strong predictor of mortality in pulmonary hypertension. Collagen accumulation is mainly responsible for PA stiffening in hypoxia-induced pulmonary hypertension (HPH) in mouse models. We hypothesized that collagen cross-linking and the type I isoform are the main determinants of large PA mechanical changes during HPH, which we tested by exposing mice that resist type I collagen degradation (Col1a1[Formula: see text] and littermate controls (Col1a1[Formula: see text] to hypoxia for 10 days with or without [Formula: see text]-aminopropionitrile (BAPN) treatment to prevent cross-link formation. Static and dynamic mechanical tests were performed on isolated PAs with smooth muscle cells (SMC) in passive and active states. Percentages of type I and III collagen were quantified by histology; total collagen content and cross-linking were measured biochemically. In the SMC passive state, for both genotypes, hypoxia tended to increase PA stiffness and damping capacity, and BAPN treatment limited these increases. These changes were correlated with collagen cross-linking ([Formula: see text]). In the SMC active state, hypoxia increased PA dynamic stiffness and BAPN had no effect in Col1a1[Formula: see text] mice ([Formula: see text]). PA stiffness did not change in Col1a1[Formula: see text] mice. Similarly, damping capacity did not change for either genotype. Type I collagen accumulated more in Col1a1[Formula: see text] mice, whereas type III collagen increased more in Col1a1[Formula: see text] mice during HPH. In summary, PA passive mechanical properties (both static and dynamic) are related to collagen cross-linking. Type I collagen turnover is critical to large PA remodeling during HPH when collagen metabolism is not mutated and type III collagen may serve as a reserve.
authors: Department of Biomedical Engineering, University of Wisconsin at Madison, 2145 ECB; 1550 Engineering Drive, Madison, WI, 53706-1609, USA.
authors: Zhijie
authors: Z
authors: Wang
authors: Roderic S
authors: RS
authors: Lakes
authors: Jens C
authors: JC
authors: Eickhoff
authors: Naomi C
authors: NC
authors: Chesler
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D003187:Compliance; D003432:Cross-Linking Reagents / Q000378:metabolism; D055119:Elastic Modulus; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology*; D066298:In Vitro Techniques; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011312:Pressure; D020033:Protein Isoforms / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D014783:Viscosity
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D003432:Cross-Linking Reagents; D020033:Protein Isoforms
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