Novel model of cardiac hypertrophy with cardiorenal dysfunction

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de Almeida Silva, Amanda ; Jensen, Leonardo ; Marques, Juliana Romeu ; Nascimento-Carvalho, Bruno ; de Souza, Leandro Eziquiel ; da Silva, Maikon Barbosa ; Moreira, Nathalia Juocys Dias ; Veras, Mariana Matera ; Waked, Dunia ; Souza, Felipe Lima ; Santinho, Mirela Aparecida Rodrigues ; Lunardon, Guilherme ; Caldini, Elia Garcia ; da Conceicao Andrade, Lucia ; Diniz, Gabriela Placona ; Irigoyen, Maria Claudia

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 15, n. 1, p. 16-pg., 2025-07-19.

Resumo

Cardiovascular diseases (CVDs) are a leading global cause of mortality. Hypertension (HTN) is a primary risk factor for developing and progressing CVDs, like cardiac hypertrophy and renal dysfunction. The use of experimental models to better understand the mechanisms linking HTN, cardiac hypertrophy, and renal dysfunction is essential. We aim to investigate whether cardiac hypertrophy induced by the aortic constriction model (TAC), combined with sodium oxalate (OXA) gavage, can serve as a novel model of cardiac hypertrophy with cardiorenal dysfunction. Four groups of C57BL/6 mice were randomized: SHAM (sham surgery and vehicle gavage), TAC (TAC surgery and vehicle gavage), OXA (sham surgery and OXA gavage), and TAC + OXA (TAC surgery and OXA gavage). In the eighth week, the TAC group exhibited elevated systolic carotid pressure, cardiac hypertrophy, increased end-diastolic volume and LV internal diameter, and renal inflammation, but did not exhibit renal dysfunction. OXA gavage intensely increased autonomic modulation as a whole (SD-PI: SHAM = 5.97 +/- 1.31 vs. OXA = 15.55 +/- 4.03, p < 0.01), caused an increase in the gene expression of SERCA2, changed the LV relaxation phase and induced renal injury, but did not cause an increase in carotid pressure or cardiac hypertrophy. The combination of TAC with OXA gavage in the TAC + OXA group caused increased carotid pressures, cardiac hypertrophy, pulmonary congestion, loss of baroreflex sensitivity (alpha index: SHAM = 3.64 +/- 1.0 vs. TAC + OXA = 0.68 +/- 0.13, p < 0.04), increased expression of SERCA2 and induced renal dysfunction. Conclusion: The combination of TAC with OXA gavage generated a novel model of cardiac hypertrophy with cardiorenal dysfunction, with a greater state of cardiac decompensation than when TAC and OXA are used separately, and caused significant renal dysfunction, a situation not observed in the TAC model or the OXA gavage model. (AU)

• Processo FAPESP: 18/19006-2 - Associação entre biomarcadores séricos, funcionais e exames de imagem na disfunção diastólica e cognitiva
• Beneficiário: Maria Claudia Costa Irigoyen
• Modalidade de apoio: Auxílio à Pesquisa - Regular