Activated myofibroblastic valve interstitial cells (VIC), identified by expression of alpha smooth muscle actin (αSMA), are thought to play a central role in mediating canine degenerative mitral valve disease (DMVD). Endothelial-to-mesenchymal cell transformation (EndMT) is a developmental mechanism active during valvulogenesis whereby endothelial cells migrate into the interstitum and transform to a mesenchymal phenotype. The study objective was to investigate whether post-developmental EndMT could be a source of high cellular density myofibroblastic VIC found in canine DMVD.
Mitral valves were collected post-mortem from 9 dogs (median age 6 years) determined by echocardiography to be free of mitral regurgitation (control group, median Whitney score = 0) and 7 dogs (median age 12 years) with DMVD (degenerative group, median Whitney score = 3). Sequential histologic sections of mitral valves were stained with Movat pentachrome and immunohistochemistry for platelet endothelial cell adhesion molecule 1 (CD31, a marker of endothelial cell phenotype), αSMA, and heparin binding-epidermal growth factor (HB-EGF).
Control and degenerative mitral valves showed positive staining for CD31 of cells on valve surfaces and within vessels of papillary muscles consistent with normal valvular and vascular endothelial cells, respectively. In degenerative mitral valves, CD31-positive cells were also found within the valve interstitum and co-localized to areas of αSMA-positive VIC suggestive of active EndMT in degenerative valves. Co-localization of HB-EGF (a mediator of endothelial cell migration) to focal areas of positive CD31 and αSMA staining was observed in some degenerative mitral valves.
Post-developmental EndMT appears to be active in canine DMVD and could be a source of myofibroblastic VIC that mediate degenerative changes.
Colorado State University
Katie has completed her Bachelor's degree, Master's degree, and most recently her DVM degree at Colorado State University. She enjoys research and teaching and hopes to specialize in cardiology. She will be pursuing these goals during her rotating internship this year at Oregon State University.
Friday, June 15
4:45 PM – 5:00 PM
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