Expression of apoptotic proteins in the pulmonary artery of dogs with pulmonary hypertension secondary to degenerative mitral valve disease

Abstract

Degenerative mitral valve disease (DMVD) is a common cause of pulmonary hypertension (PH) in dogs. Medial thickening of the pulmonary artery is a common histopathological change in PH. The cause of medial thickening could be a decrease in apoptosis of pulmonary arterial smooth muscle cells (SMCs). This study aimed to detect the expression of apoptosis-related proteins in the pulmonary artery of dogs with PH secondary to DMVD (DMVD+PH) compared with DMVD without PH (DMVD) and healthy dogs (control). Lung samples were collected from three groups, including the control (n = 5), DMVD (n = 7) and DMVD+PH (n = 7) groups. Masson trichrome, α-SMA and apoptotic proteins including Bax, Bcl2 and caspase-3 and -8 were stained. The results showed that the percentage of medial thickness (%MT) and the average number of pulmonary arterial SMCs were greater in the DMVD and DMVD+PH groups than in the control group, and they were greatest in the DMVD+PH group. Bax, Bcl2, and caspase-3 and -8 were mainly expressed in the medial layer of the pulmonary artery. The percentage of Bax and caspase-3 and -8 positive cells was higher in the DMVD group than in the DMVD+PH group, whereas the percentage of Bcl2 positive cells was increased in the DMVD+PH group. These results suggested that the pro-apoptotic activity of pulmonary arterial SMCs occurred mainly in the DMVD group and decreased dramatically in the DMVD+PH group. In conclusion, an increase in medial thickness in dogs with PH secondary to DMVD may relate to a decrease in pro-apoptotic activity of pulmonary arterial SMCs.

Keywords: Apoptosis; Degenerative mitral valve disease; Medial thickening; Pulmonary hypertension; Smooth muscle cells.