Cold exposure aggravates pulmonary arterial hypertension through increased miR-146a-5p, miR-155-5p and cytokines TNF-α, IL-1β, and IL-6.

Autor: Sánchez-Gloria JL; Sección de Estudios de posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico city 11340, Mexico; Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico., Carbó R; Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico., Buelna-Chontal M; Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico., Osorio-Alonso H; Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico., Henández-Díazcouder A; Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico; Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico city 09340, Mexico., de la Fuente-León RL; Posgrado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México, Mexico., Sandoval J; Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico., Sánchez F; DPAA, Universidad Autónoma Metropolitana-Xochimilco, Mexico city 04960, Mexico., Rubio-Gayosso I; Sección de Estudios de posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico city 11340, Mexico., Sánchez-Muñoz F; Sección de Estudios de posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico city 11340, Mexico; Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico city 14080, Mexico. Electronic address: fausto.sanchez@cardiologia.org.mx.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Dec 15; Vol. 287, pp. 120091. Date of Electronic Publication: 2021 Oct 28.
DOI: 10.1016/j.lfs.2021.120091
Abstrakt: 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.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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