Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentPaul R. Hiebert 1,2 , Thomas Abraham 1 , Sara Pazooki 1 , Wendy A. Boivin 1,2 ,Hongyan Zhao 1 , David J. Granville 1,21Providence Heart + Lung Institute at St. Paul’s Hospital, 2 Department of Pathology andLaboratory Medicine, University of British ColumbiaAbstract # 44Paul Hiebertskin aging as an indicator of cardiovascular health inapolipoprotein E knockout miceBackround/ObjectivesThe skin can be a useful indicator of cardiovascular aging and disease. Several studies suggest that markers of skinaging such as advanced glycation end products as well as skin conditions such as psoriasis and early onset alopecia areassociated with increased risk of cardiovascular events including heart attack and stroke. We and others have observedan inflammatory skin aging phenotype in apolipoprotein E (apoE) deficient mice, an established animal model ofatherosclerosis, which increases in severity when mice are fed a high fat diet. The purpose of the present study is tocharacterize the effects of apoE deficiency as well as diet on skin aging and disease in order to better understand thelink between skin and cardiovascular health.MethodsWild type C57BL/6 and apoE knockout (apoE-KO) mice were grown to 0, 5, 15 or 30 weeks on either a regularchow or high fat diet. H&E, picrosirius red and luna stains were used to assess morphology and extracellular matrixchanges in formalin fixed skin sections. Multi-photon microscopy was also used to examine collagen organizationand morphology in ex vivo mouse skin samples. Immunostaining for the cytotoxic protease granzyme B was alsoperformed.ResultsApoE-KO mice exhibited signs of frailty, hair loss and increased morbidity compared to wild type controls. H&Estaining demonstrated a reduction in skin thickness along with increased inflammation and evidence of xanthomatouslesions while picrosirus red and luna staining revealed marked differences in the collagen and elastin contentrespectively in apoE-KO mice compared to wild type controls. Multi-photon microscopy of thick skin sectionsrevealed a decrease in collagen density and organization in apoE-KO mice compared to controls. Considerablegranzyme B expression was also observed in the skin of apoE-KO mice. These observations became increasinglyevident with age and when mice were fed a high fat diet.ConclusionThese results suggest that, similar to its effects on plaque formation and destabilization, a high fat diet acceleratesaging and disease of the skin in apoE-KO mice and further supports the concept of assessing the skin as a marker ofcardiovascular health.Poster Presentations * 2 0 1 055