The impact of complement C1q/tumor necrosis factor-related protein 6-mediated cardiomyocyte pyroptosis on myocardial fibrosis in rats with myocardial infarction.

Impacto de la piroptosis de cardiomiocitos mediada por CTRP6 en la fibrosis miocárdica en ratas con infarto de miocardio.

• Qiu Zhang Department of Cardiology, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, JiangSu, China. https://orcid.org/0009-0002-5874-7484
• Xin Chen Department of Cardiology, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, JiangSu, China. https://orcid.org/0009-0005-6572-9323
• Hao Pan Department of Cardiology, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, JiangSu, China. https://orcid.org/0009-0005-4335-9325
• Zengguang Chen Department of Cardiology, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, JiangSu, China. https://orcid.org/0000-0002-0895-3215

DOI: https://doi.org/10.54817/IC.v67n1a02

Palabras clave: Infarto de Miocardio, Piroptosis, fibrosis, Respuesta Inflamatoria

Resumen

La proteína 6 relacionada con el factor de necrosis del comple- mento C1q/tumor (CTRP6) tiene propiedades antiinflamatorias y reguladoras metabólicas, pero su papel en la reducción de la fibrosis del miocardio postinfar- to (MI) mediante la inhibición de la piroptosis no está claro. Este estudio inves- tigó si el CTRP6 mejora la fibrosis miocárdica post-MI y la disfunción cardíaca al suprimir la piroptosis de cardiomiocitos mediante la vía NLRP3/caspasa-1/ GSDMD. Treinta ratas Sprague-Dawley se asignaron aleatoriamente a grupos operados con simulación (Sham), modelo MI (MI) o tratados con CTRP6 (MI + CTRP6). El MI fue inducido por ligadura de la arteria coronaria descendente an- terior izquierda. Las ratas MI+CTRP6 recibieron CTRP6 recombinante por vía subcutánea diaria (0,2 mg/kg) a partir del día 3 tras la cirugía durante 28 días. La función cardíaca (ecocardiografía), los marcadores de fibrosis, las proteínas relacionadas con la piroptosis y las citocinas inflamatorias se evaluaron median- te transferencia Western, tinción de Masson y ELISA. La expresión de CTRP6 fue menor en MI que en Sham (p<0,05). El tratamiento con CTRP6 restableció su expresión, redujo los marcadores de fibrosis y de deposición de colágeno, y mejoró la función cardíaca (p<0,05). También disminuyó la regulación de las citocinas proinflamatorias y  aumentó  la  regulación  antiinflamatoria  (p<0,05). El CTRP6 protege contra la fibrosis miocárdica post-MI inhibiendo la piroptosis de cardiomiocitos a través de la vía NLRP3/caspasa-1/GSDMD, reduciendo las citocinas proinflamatorias y la activación de fibroblastos.

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