TY - JOUR
T1 - Cold exposure aggravates pulmonary arterial hypertension through increased miR-146a-5p, miR-155-5p and cytokines TNF-α, IL-1β, and IL-6
AU - Sánchez-Gloria, José L.
AU - Carbó, Roxana
AU - Buelna-Chontal, Mabel
AU - Osorio-Alonso, Horacio
AU - Henández-Díazcouder, Adrián
AU - de la Fuente-León, Rosa Luz
AU - Sandoval, Julio
AU - Sánchez, Fausto
AU - Rubio-Gayosso, I.
AU - Sánchez-Muñoz, Fausto
N1 - Publisher Copyright:
© 2021
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Background: Cold temperatures can aggravate pulmonary diseases and promote pulmonary arterial hypertension (PAH); however, the underlying mechanism has not been fully explored. Aim: To explore the effect of chronic cold exposure on the production of inflammatory cytokines and microRNAs (miRNAs) in a monocrotaline (MCT)-induced PAH model. Methods: Male Sprague Dawley rats were divided into a Control (23.5 ± 2 °C), Cold (5.0 ± 1 °C for ten days), MCT (60 mg/kg body weight i.p.), and MCT + Cold (ten days of cold exposure after 3 weeks of MCT injection). Hemodynamic parameters, right ventricle (RV) hypertrophy, and pulmonary arterial medial wall thickness were determined. IL-1β, IL-6, and TNF-α levels were determined using western blotting. miR-21-5p and -3p, miR-146a-5p and -3p, and miR-155-5p and -3p and plasma extracellular vesicles (EVs) and mRNA expression of Cd68, Cd163, Bmpr2, Smad5, Tgfbr2, and Smad3 were determined using RT-qPCR. Results: The MCT + Cold group had aggravated RV hypertrophy hemodynamic parameters, and pulmonary arterial medial wall thickness. In lungs of the MCT + Cold, group the protein levels of TNF-α, IL-1β, and IL-6 were higher than those in the MCT group. The mRNA expression of Cd68 and Cd163 were higher in the MCT + Cold group. miR-146a-5p and miR-155-5p levels were higher in the plasma EVs and lungs of the MCT + Cold group. Cold exposure promoted a greater decrease in miR-21-5p, Bmpr2, Smad5, Tgfbr2, and Smad3 mRNA expression in lungs of the MCT + Cold group. Conclusion: Cold exposure aggravates MCT-induced PAH with an increase in inflammatory marker and miRNA levels in the plasma EVs and lungs.
AB - Background: Cold temperatures can aggravate pulmonary diseases and promote pulmonary arterial hypertension (PAH); however, the underlying mechanism has not been fully explored. Aim: To explore the effect of chronic cold exposure on the production of inflammatory cytokines and microRNAs (miRNAs) in a monocrotaline (MCT)-induced PAH model. Methods: Male Sprague Dawley rats were divided into a Control (23.5 ± 2 °C), Cold (5.0 ± 1 °C for ten days), MCT (60 mg/kg body weight i.p.), and MCT + Cold (ten days of cold exposure after 3 weeks of MCT injection). Hemodynamic parameters, right ventricle (RV) hypertrophy, and pulmonary arterial medial wall thickness were determined. IL-1β, IL-6, and TNF-α levels were determined using western blotting. miR-21-5p and -3p, miR-146a-5p and -3p, and miR-155-5p and -3p and plasma extracellular vesicles (EVs) and mRNA expression of Cd68, Cd163, Bmpr2, Smad5, Tgfbr2, and Smad3 were determined using RT-qPCR. Results: The MCT + Cold group had aggravated RV hypertrophy hemodynamic parameters, and pulmonary arterial medial wall thickness. In lungs of the MCT + Cold, group the protein levels of TNF-α, IL-1β, and IL-6 were higher than those in the MCT group. The mRNA expression of Cd68 and Cd163 were higher in the MCT + Cold group. miR-146a-5p and miR-155-5p levels were higher in the plasma EVs and lungs of the MCT + Cold group. Cold exposure promoted a greater decrease in miR-21-5p, Bmpr2, Smad5, Tgfbr2, and Smad3 mRNA expression in lungs of the MCT + Cold group. Conclusion: Cold exposure aggravates MCT-induced PAH with an increase in inflammatory marker and miRNA levels in the plasma EVs and lungs.
KW - Cold exposure
KW - Inflammation
KW - PAH
KW - microRNA
UR - http://www.scopus.com/inward/record.url?scp=85118508074&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2021.120091
DO - 10.1016/j.lfs.2021.120091
M3 - Artículo
C2 - 34717910
AN - SCOPUS:85118508074
SN - 0024-3205
VL - 287
JO - Life Sciences
JF - Life Sciences
M1 - 120091
ER -