The role of the extracellular matrix protein Perlecan in the arterial wall (546.10)

Abstract

Perlecan (HSPG2; Perl) is expressed in all basement membranes and cartilage. Perl has been reported to have anti‐atherogenic activity; however, its role in the aortic wall is unknown. In this report, we analyzed the structure of the aortic wall in Perlecan deficient mice (HSPG2‐/‐‐Tg).Previously, we created the lethality rescued HSPG2‐/‐‐Tg mice model. Aorta samples were prepared from the thoracic aorta of HSPG2‐/‐‐Tg (Perl KO) and control HSPG+/+‐Tg mice. We analyzed the histology of these aortic tissues by Elastica Van Gieson (EVG) staining, immunohistochemistry (IHC), and electron microscope (EM). In IHC, we observed that perlecan is localized at the intersection between elastin and fibrillin‐1. EVG staining showed no difference in aorta histology between Perl KO and control mice, however, EM analysis showed that the elastic fibers in Perl KO mice were partially torn and thinner. In addition, we found that Perl KO mice had an aortic dissection with a frequency of about 15% in 10‐weeks mice. Real‐time PCR analysis showed no significant differences in the expression of genes for the major components of elastic fibers and matrix metalloproteinases (MMPs).These results suggest that Perl is likely to contribute to the maintainance of elastic fibers strength against mechanical stress, such as blood flow, vasodilation, and contraction.