Abstract
BackgroundFibulin-4 is an extracellular matrix protein expressed by vascular smooth muscle cells that is essential for maintaining arterial integrity. Fibulin-4−/− mice die just before birth due to arterial hemorrhage, but fibulin-4+/− mice appear to be outwardly normal. Experiments were therefore performed to determine whether fibulin-4+/− mice display arterial pathologies on a microscopic scale. After preliminary experiments were performed, a second purpose developed, which was to test the hypothesis that any observed pathologies would be ameliorated by housing the animals in enriched cages.MethodologyFibulin-4+/− and wild-type mice were housed either four/cage in standard cages or two per cage in larger cages, each cage containing a tunnel and a wheel. After three weeks the mice were sacrificed, and the aortas perfusion-fixed and excised for light and electron microscopy.Principle FindingsWhen the mice were in standard cages, localized regions of disorganized extracellular matrix and collagen fibers consistently appeared between some of the medial smooth muscle cells in the fibulin-4+/− mice. In the wild-type mice, the smooth muscle cells were closely connected to each other and the media was more compact. The number of disorganized regions per square mm was significantly greater for fibulin-4+/− mice (172±43 (SEM)) than for wild-type mice (15±8) (p<0.01, n = 8). When the mice were in enriched cages, the fibulin-4+/− mice showed significantly fewer disorganized regions than those in standard cages (35±12) (p<0.05, n = 8). The wild type mice also showed fewer disorganized regions (3±2), but this difference was not significant.ConclusionsThese results indicate that arterial pathologies manifested in fibulin-4+/− mice can be reduced by enriching the housing conditions, and imply that appropriate environments may counteract the effects of some genetic deficiencies.
Highlights
The mechanical properties of the vascular wall are mainly determined by elastin and collagen with a contribution from smooth muscle cells
Numbers of gaps were compared using the Mann-Whitney Rank Sum test because not all data groups passed the normality test. Both the wild-type and fibulin-4+/2 age-matched mice were significantly lighter when housed in the enriched cages compared to the standard cages (p,0.001)
Mice housed in the standard cages showed very large quantities of adipose fat around the aorta, whereas those housed in the enriched cages did not
Summary
The mechanical properties of the vascular wall are mainly determined by elastin and collagen with a contribution from smooth muscle cells. Twenty years ago, a 6-member family of proteins was discovered: the fibulin family These fibulins were hypothesized to function as intramolecular bridges, stabilizing the organization of other ECM structures, such as elastic and collagen fibers [2]. Fibulin-4 is localized in the aortic media and is essential for maintaining arterial integrity since homozygous fibulin-4 knockout mice die just before birth due to arterial hemorrhage. In these mice, elastin cross-links are diminished and the elastic lamellae are fragmented [5]. When the mice were in standard cages, localized regions of disorganized extracellular matrix and collagen fibers consistently appeared between some of the medial smooth muscle cells in the fibulin-4+/2 mice. These results indicate that arterial pathologies manifested in fibulin-4+/2 mice can be reduced by enriching the housing conditions, and imply that appropriate environments may counteract the effects of some genetic deficiencies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
