Artículo
Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice
Fontana Estevez, Florencia Sofía
; Betazza, Celeste; Miksztowicz, Verónica Julieta
; Seropian, Ignacio Miguel; Silva, Mauro Gastón; Penas, Federico Nicolás
; Touceda, Vanessa Michelle; Selser, Carolina; Villaverde, Alejo; Goren, Nora Beatriz
; Cianciulli, Tomás Francisco; Medina, Vanina Araceli
; Morales, Celina; Gironacci, Mariela Mercedes
; González, Germán Esteban
Fecha de publicación:
08/2022
Editorial:
Karger
Revista:
Cellular Physiology and Biochemistry
ISSN:
1015-8987
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Background/Aims: Aging is accompanied by progressive and adverse cardiac remodeling characterized by myocardial hypertrophy, fibrosis, and dysfunction. We previously reported that galectin-3 (Gal-3) is a critical regulator of inflammation and fibrosis associated with hypertensive heart disease and myocardial infarction. Nevertheless, the role and mechanism of Gal-3 in age-related cardiac remodeling have not been previously investigated. We hypothesized that Gal-3 plays a critical role in cardiac aging and that its deficiency exacerbates the underlying mechanisms of myocardial hypertrophy and fibrosis. Methods: Male C57BL/6 (control) (n=24) and Gal-3 knockout (KO) (n=29) mice were studied at 24 months of age to evaluate the role of Gal-3 in cardiac aging. We assessed 1) survival rate; 2) systolic blood pressure (SBP) by plethysmography; 3) myocardial hypertrophy, apoptosis, and fibrosis by quantification of histological and immunohistochemical analysis; 4) cardiac expression of angiotensin (Ang) II, Ang (1–7) by Radioimmunoassay; 5) transforming growth factor-β (TGF-β), sirtuin (SIRT) 1, SIRT 7 and metalloproteinase 9 (MMP-9) by RT-qPCR and 6) ventricular remodeling and function by echocardiography. Results: We found that aged Gal-3 KO mice had a lower survival rate and exhibited exacerbated myocardial hypertrophy and fibrosis without changes in SBP. Similarly, myocardial apoptosis and MMP-9 mRNA expression was significantly increased in the hearts of Gal-3 KO mice compared to controls. Additionally, cardiac Ang II and TGF-β expression were higher in aged Gal-3 KO mice while SIRT1 and SIRT7 expression were reduced. Conclusion: Our findings strongly suggest that Gal-3 is involved in age-related cardiac remodeling by regulating critical mechanisms associated with the development of pathological hypertrophy. The gene deletion of Gal-3 reduced the lifespan and markedly increased age-dependent mechanisms of myocardial hypertrophy, apoptosis, and fibrosis, including Ang-II, TGF-β, and MMP-9. At the same time, there was diminished cardiac-specific expression of SIRT1 and SIRT7, which are extensively implicated in delaying age-dependent cardiomyopathies.
Palabras clave:
AGING
,
CARDIAC AGING
,
FIBROSIS
,
GALECTIN-3
,
HYPERTROPHY
Archivos asociados
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Identificadores
Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(INBIRS)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Fontana Estevez, Florencia Sofía; Betazza, Celeste; Miksztowicz, Verónica Julieta; Seropian, Ignacio Miguel; Silva, Mauro Gastón; et al.; Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice; Karger; Cellular Physiology and Biochemistry; 56; 4; 8-2022; 353-366
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