#39 - Cardiac Cellular Senescence and Igfbp-7 Associated With Cardiovascular Damage in Experimental Models of Masld, Metald and Ald

Introduction and Objectives Metabolic dysfunction associated steatotic liver disease (MASLD), its variant with alcohol consumption (MetALD), and alcohol related liver disease (ALD) are associated with an increased cardiovascular risk (MASLD with a stronger association); however, the mechanisms of damage involved are unknown. Senescence constitutes a response to cellular damage and the protein IGFBP-7, described as an inducer, could be involved in the cardiac alterations associated with these liver diseases. Our objective was to evaluate cardiac cellular senescence and IGFBP-7 concentrations in experimental murine models of MASLD, MetALD and ALD. Patients and Methods Ten-week-old C57BL/6 mice (female and male) were divided into four groups: C (Control), HF (high-fat diet), OH (20% ethanol), and HFOH (HF and OH) for four months. Subsequently, hearts were collected (females in diestrus) and senescence associated -galactosidase was evaluated in frozen histological sections. IGFBP-7 was quantified from cardiac protein extract by ELISA. Statistical analysis was performed using Kruskal-Wallis followed by Dunn or Mann-Whitney; data expressed as median and interquartile range (25-75). Results In females, senescence associated -galactosidase in the heart increased significantly in the HFOH group compared to C (p=0.039). In males, IGFBP-7 quantification showed an increase in the OH group compared to C (p=0.03). Conclusions Consumption of a high-fat diet and ethanol promotes cardiac cellular senescence, particularly in females, suggesting possible sexual dimorphism. In males, IGFBP-7 is overexpressed with ethanol consumption. These findings suggest cellular senescence as a mechanism involved in the increased cardiovascular risk.