Apoptosis and abundance of Bcl-2 family and transforming growth factor beta 1 signaling proteins in canine myxomatous mitral valves

作者：Surachetpong Sirilak^*; Jiranantasak Treenate; Rungsipipat Anudep; Orton E Christopher

来源：Journal of Veterinary Cardiology, 2013, 15(3): 171-180.

DOI：10.1016/j.jvc.2013.02.005

• Cell death
• Dogs
• Mitral valve
• Signaling
• Valve interstitial cells

Objectives: To determine the percentage of cells undergoing apoptosis within canine myxomatous valves and to evaluate whether TGF beta 1 can be implicated as an anti-apoptosic signal through the Bcl-2 family of signaling proteins. %26lt;br%26gt;Animals: Post-mortem mitral valve leaflets harvested from 5 normal dogs, 5 dogs with early-stage myxomatous mitral valve disease (MMVD), and 5 dogs with late-stage MMVD. %26lt;br%26gt;Materials and methods: The number of cells expressing cleaved caspase-3, DNA fragmentation (TUNEL marker) and apoptotic bodies were evaluated as a measure of apoptosis. To evaluate the relationship between TGF beta 1 signaling and apoptosis, the abundance of activated TGF beta 1 signaling protein, phosphorylated Smad 2/3 (p-Smad 2/3), and Bcl-2 family proteins (pro-apoptotic Bax and anti-apoptotic Bcl-2) was determined by immunohistochemistry. %26lt;br%26gt;Results: Cells in normal and both stages of MMVD expressed the TUNEL marker and cleaved caspase-3, but not apoptotic bodies. The percentage of TUNEL marker and cleaved caspase-3 positive nuclei was not significantly different between groups of dogs (p%26gt;0.05). P-Smad 2/3 and Bax were more abundant in myxomatous mitral valves while Bcl-2 was less abundant. P-Smad 2/3 primarily increased in the atrialis layer and was abundantly increased only in late-stage MMVD. %26lt;br%26gt;Conclusions: These data suggest that interstitial cells in MMVD are in a pro-apoptotic condition; however, they do not execute apoptosis. Thus, apoptosis does not explain differences in cellular density in canine MMVD. TGF beta 1 signaling through the canonical SMAD pathway is increased in myxomatous mitral valves, but does not apparently mediate interstitial cell apoptosis in canine MMVD.

• 出版日期2013-9