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This Article Full Text Full Text (PDF) All Versions of this Article: 106/6/2002    most recent 90777.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tuday, E. C. Articles by Berkowitz, D. E. PubMed PubMed Citation Articles by Tuday, E. C. Articles by Berkowitz, D. E.

Simulated microgravity-induced aortic remodeling

¹Department of Biomedical Engineering and ²Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Submitted 17 June 2008 ; accepted in final form 18 March 2009

We have previously shown that microgravity and simulated microgravity induce an increase in human and rat aortic stiffness. We attempted to elucidate the mechanism(s) responsible for this increase in stiffness. We hypothesize that an alteration in vessel wall collagen or elastin content or in extracellular matrix (ECM) cross-linking either individually or in a combination is responsible for the increased vessel stiffness. Rats underwent hindlimb unweighting (HLU) for a period of 7 days to simulate microgravity. The contribution of ECM cross-linking to the vessel wall stiffness was evaluated by measuring aortic pulse wave velocity following inhibition of the cross-linking enzymes lysyl oxidase (LOX) and transglutaminase (tTG) and the nonenzymatic advanced glycation end product cross-linking pathway during HLU. Aortic collagen and elastin content was quantified using established colorimetric assays. Collagen subtype composition was determined via immunofluorescent staining. The increase in aortic pulse wave velocity after HLU was significantly attenuated in the LOX and tTG inhibition groups compared with saline (1.13 ± 0.11 vs. 3.00 ± 0.15 m/s, LOX vs. saline, P < 0.001; 1.16 ± 0.25 vs. 3.00 ± 0.15 m/s, tTG vs. saline, P < 0.001). Hydroxyproline content, a measure of collagen content, was increased in all groups after HLU (2.01 ± 0.62 vs. 3.69 ± 0.68% dry weight, non-HLU vs. HLU, P = 0.009). Collagen subtype composition and aortic elastin content were not altered by HLU. Together, these data indicate that HLU-induced increases in aortic stiffness are due to both increased aortic collagen content and enzyme cross-linking activity.

arterial stiffness; hindlimb unweighting; vascular remodeling