Saturday, February 18, 2012
Exhibit Hall A-B1 (VCC West Building)
Background: Alopecia areata (AA) is a non-scarring, inflammatory cell-mediated, autoimmune hair loss disease that has a 1.7% lifetime risk to develop in individuals of both genders and all age groups. AA can begin as patchy loss of scalp hair, but as the disease becomes chronic, one may lose all scalp hair (Totalis) or even body hair (Universalis). AA is not life threatening alone but it can adversely affect the quality of life due to undesirable appearance and other autoimmune diseases that are often associated with it. In previously published studies, AA mice exhibited increased adrenocorticotrophic hormone (ACTH) expression and aberrantly responded to psychological stress. My preliminary results showed significantly heavier hearts in AA affected mice. The aberrant stress response could potentially affect the function of multiple organs such as the heart in AA affected individuals. The associations of AA with heart diseases have never been studied. As such, my goal is to investigate the potential effects of chronic AA on heart health and physiology. Methods: AA affected female C3H/HeJ mice were generated by skin grafting AA affected skin from a donor mouse; control mice were sham-grafted. Heart and skin sections were obtained for quantitative RT-PCR (qPCR) and histology to look at gene and protein expression in AA mice compared to the controls. Masson's Trichrome Stain was used to visualize collagen deposition in the heart sections as well as calculating the relative thickness of blood vessels. Blood was collected and subjected to ELISA assay for heart remodelling marker cardiac troponin I (cTnI). Atria and ventricles were micro-dissected for short-term (72hrs) organ culture with increasing concentration of ACTH (0μM, 0.1μM, 1μM, 2μM). Results: Gene profiling using qPCR showed a significant elevation of IL18, IL18 binding protein (IL18bp) and IL18 receptor (IL18r1) in the skin and heart tissues of AA mice. Possible IL18 induced fibrosis was observed with collagen staining where AA mouse hearts showed increased collagen infiltration into the blood vessels as well as perivascular collagen deposition and blood vessel wall thinning. Immunohistochemistry of heart sections revealed a higher intensity and localization of IL18 in the atria of AA mice only. Higher level of cTnI was observed in AA mouse serum and significantly increased after ACTH treatment indicating possible adverse effects of ACTH on hearts. qPCR analysis after ACTH treatment revealed significant elevation of IL18 at 1μM and 2μM as well as dose dependent decrease of IL18bp. Conclusions: The development of AA may be associated with increased production of ACTH which may result in damage in the heart via modulation of IL18 expression, especially in the atria. Elevation of cTnI, indicating heart damage, was also observed with increase of ACTH. My results suggest that dysregulated stress hormones in chronic AA may lead to heart failure and could imply that additional care is needed for AA patients.