In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension

• Autor(a) principal: Batah, Sabrina Setembre
• Data de Publicação: 2020
• Outros Autores: Alda, Maiara Almeida, Lopes Roslindo Figueira, Rebeca Rodrigues, Cruvinel, Heloisa R. [UNESP], Rodrigues da Silva, Luis Perdona [UNESP], Machado-Rugolo, Juliana [UNESP], Velosa, Ana Paula, Teodoro, Walcy Rosolia, Balancin, Marcelo, Silva, Pedro Leme, Capelozzi, Vera Luiza, Fabro, Alexandre Todorovic
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1159/000510048; http://hdl.handle.net/11449/210416
• topic: Collagen type V; Collagen type I; Monocrotaline; Pulmonary arterial hypertension; Immunofluorescence; Interleukin-6; Interleukin-17

Several studies have reported the pathophysiologic and molecular mechanisms responsible for pulmonary arterial hypertension (PAH). However, the in situ evidence of collagen V (Col V) and interleukin-17 (IL-17)/interleukin-6 (IL-6) activation in PAH has not been fully elucidated. We analyzed the effects of collagen I (Col I), Col V, IL-6, and IL-17 on vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty male Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, whereas the control group (CTRL) received saline. On day 21, the pulmonary blood pressure (PAP) and right ventricular systolic pressure (RVSP) were determined. Lung histology (smooth muscle cell proliferation [alpha-smooth muscle actin; alpha-SMA] and periadventitial fibrosis), immunofluorescence (Col I, Col V, and alpha-SMA), immunohistochemistry (IL-6, IL-17, and transforming growth factor-beta [TGF-beta]), and transmission electron microscopy to detect fibronexus were evaluated. The RVSP (40 +/- 2 vs. 24 +/- 1 mm Hg, respectively; p < 0.0001), right ventricle hypertrophy index (65 +/- 9 and 25 +/- 5%, respectively; p < 0.0001), vascular periadventitial Col I and Col V, smooth muscle cell alpha-SMA+, fibronexus, IL-6, IL-17, and TGF-beta were higher in the MCT group than in the CTRL group. In conclusion, our findings indicate in situ evidence of Col V and IL-6/IL-17 activation in vascular remodeling and suggest that increase of Col V may yield potential therapeutic targets for treating patients with PAH.