Sex-dependent differences on the impact of anti-inflammatory treatment in the progression of coronary artery disease in a murine model of lethal ischemic heart disease induced by diet

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Cardiovascular risk differs significantly between adult men and women. Therefore, it is expected that different treatments may affect both groups differently. We aim to compare sexdependent differences on survival and systemic inflammation in response to anti-inflammatory treatment using a diet-induced myocardial infarction mouse model. Method. Male and female SR-B1−/−ApoER61h/h mice, aged 2-3 months, were randomly assigned into two groups: Control (HFD-Control) and minocycline (HFD-MIN). Atherosclerosis was induced by feeding an atherogenic diet (15% fat, 1.25% cholesterol, 0.5% cholate). Minocycline was administered in the drinking water at a dose of 0.05 mg/mL. Female mice had a slightly better survival than male mice when fed an HFD (p=0.12). Minocycline improved survival in male by 35% (p=0.006) and by 33% in female p=0.01), without affecting total cholesterol levels. Male mice fed with HFD tended to have higher IL-6 levels than female mice (p=0.08). Minocycline significantly reduced IL-6 levels (p=0.04) and Ly6Chigh (p=0.006) and increased the Ly6Clow subset (p=0.006). Male and female fed with HFD clustered in different groups by analyzing inflammatory parameters by PCA; however, after minocycline intervention, were indistinguishable. High fat diet decreased survival and caused early death in this animal model, however, females had slightly better survival than male mice. Minocycline treatment improved survival in both groups although it did not affect their cholesterol levels. Males showed higher inflammatory serum biomarkers than females, and minocycline treatment showed a higher impact on systemic anti-inflammation in male mice than female, by reducing plasma IL-6 levels and shifting toward a more "reparative" phenotype on circulating monocyte subsets.
Tesis (Magíster en Investigación en Ciencias de la Salud)--Pontificia Universidad Católica de Chile, 2023.
Atherosclerosis, Gender, Inflammation, Monocytes/macrophages