Sakarin Siriwan, Rungsipipat Anudep, Surachetpong Sirilak Disatian
Department of Veterinary Medicine, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
Companion Animal Cancer Research Unit, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
Res Vet Sci. 2022 Jul;145:238-247. doi: 10.1016/j.rvsc.2022.03.006. Epub 2022 Mar 8.
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.
退行性二尖瓣疾病（DMVD）是犬肺动脉高压（PH）的常见病因。肺动脉中层增厚是PH常见的组织病理学变化。中层增厚的原因可能是肺动脉平滑肌细胞（SMC）凋亡减少。本研究旨在检测继发于DMVD的PH犬（DMVD+PH）与无PH的DMVD犬（DMVD）及健康犬（对照）肺动脉中凋亡相关蛋白的表达。从三组采集肺样本，包括对照组（n = 5）、DMVD组（n = 7）和DMVD+PH组（n = 7）。进行了Masson三色染色、α-SMA染色以及包括Bax、Bcl2、caspase-3和-8在内的凋亡蛋白染色。结果显示，DMVD组和DMVD+PH组的中层厚度百分比（%MT）和肺动脉SMC平均数量均高于对照组，且在DMVD+PH组中最高。Bax、Bcl2、caspase-3和-8主要表达于肺动脉中层。DMVD组中Bax、caspase-3和-8阳性细胞百分比高于DMVD+PH组，而DMVD+PH组中Bcl2阳性细胞百分比增加。这些结果表明，肺动脉SMC的促凋亡活性主要发生在DMVD组，而在DMVD+PH组中显著降低。总之，继发于DMVD的PH犬中层厚度增加可能与肺动脉SMC促凋亡活性降低有关。
