Expression of Transforming Growth Factor-β1, -β2 and -β3 in Normal and Diseased Canine Mitral Valves

Alpha-smooth muscle actin and serotonin receptors 2A and 2B in dogs with myxomatous mitral valve disease

“…However, technical challenges with antigen de-masking arose in the lab and along with antibody specificity this might also account for differences between qPCR and IHC results, and between the current and past studies. The strong marginal localization of α-SMA in the present study is in agreement with the increased presence of TGF-β and activated VIC in the vicinity of carcinoid nodules in humans (Jian et al, 2002) and a similar pattern has been reported in dogs (Aupperle et al, 2008). The perinodular location of α-SMA positive cells is also in agreement with the description of inactive stromal cells (VIC) in the central regions of pronounced myxomatous nodules (Aupperle et al, 2008(Aupperle et al, , 2009a.…”

“…The strong marginal localization of α-SMA in the present study is in agreement with the increased presence of TGF-β and activated VIC in the vicinity of carcinoid nodules in humans (Jian et al, 2002) and a similar pattern has been reported in dogs (Aupperle et al, 2008). The perinodular location of α-SMA positive cells is also in agreement with the description of inactive stromal cells (VIC) in the central regions of pronounced myxomatous nodules (Aupperle et al, 2008(Aupperle et al, , 2009a. It has been suggested that the increased production of basement membrane material like laminin and fibronectin in the marginal zones creates a barrier to myofibroblast migration (Aupperle et al, 2009b).…”

“…It has been suggested that the increased production of basement membrane material like laminin and fibronectin in the marginal zones creates a barrier to myofibroblast migration (Aupperle et al, 2009b). Moreover, increased presence of tissue inhibitors of metalloproteinases (TIMPs) centrally in nodules favors latent TGF-β with resulting downregulation of myofibroblasts (Aupperle et al, 2008). Another study reported the presence of not only latent TGF-β1 but also TGF-β receptors I and II throughout myxomatous lesions indicating active signaling (Disatian and Orton, 2009).…”

Signaling pathways in mitral valve degeneration

“…54 Several studies have demonstrated strong overexpression of TGFb isoforms in canine degenerative mitral valves. 47,55,56 Our group has also reported increased abundance of TGFb RI and RII in canine degenerative mitral valves. 47 TGFb1 mediates myofibroblast transformation (a-SMA expression) in cultured VIC in a concentrationdependent manner, and is synergistic with tensile stress in causing this effect.…”

Emerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data

“…An efficient treatment of these mice was obtained with a TGF-β neutralizing antibody [13] or with losartan, a selective angiotensin II type 1 receptor antagonist that interacts with TGF-β signaling [14], further supporting the involvement of excessive TGF-β signaling in MMV. With the exception of one single study showing a high expression of TGF-β1 and TGF-β3 in canine MMV [15], no study had shown so far an association between TGF-β dysregulation and idiopathic MMV in humans.…”