We aimed to test the effect of hydroxychloroquine (HCQ) treatment on atherosclerosis and plasma lipids in apolipoprotein E deficient (ApoE Forty-seven (47) mice were divided into two treatment groups: Show more
We aimed to test the effect of hydroxychloroquine (HCQ) treatment on atherosclerosis and plasma lipids in apolipoprotein E deficient (ApoE Forty-seven (47) mice were divided into two treatment groups: an HCQ group administered 10 mg/kg/day in drinking water for 16 weeks and a control group with no HCQ. All mice were maintained on a standard chow diet containing 5% fat and had free access to water. At 32 weeks of age, blood was drawn for plasma lipid determination and the proximal aorta was removed to measure the atherosclerotic area and evaluate the expression of eNOS and HIF-1α by immunohistochemistry. The HCQ group consisted of 16 mice (10 males, six females), while the control group consisted of 31 mice (17 males, 14 females). HCQ significantly reduced the atherosclerotic area (mm HCQ reduces aortic atherosclerosis in ApoE Show less
Hydroxychloroquine (HCQ) has been associated with lower incidence of cardiovascular events in patients with autoimmune diseases and atherosclerosis progression in mouse models. Our study aimed at inve Show more
Hydroxychloroquine (HCQ) has been associated with lower incidence of cardiovascular events in patients with autoimmune diseases and atherosclerosis progression in mouse models. Our study aimed at investigating the effect of HCQ on autophagy and neutrophil extracellular trap (NET) formation in aortas of ApoE-/- mice. ApoE-/- mice were treated with 10 mg/kg/day HCQ for 16 weeks. The aortas were examined histologically, while immunofluorescence staining and confocal microscopy were performed to identify the co-localization of myeloperoxidase (MPO) with DNA or microtubule-associated protein 1A/1B-light chain 3B (LC3B) as markers of NET formation and autophagy, respectively. Among 52 ApoE-/- mice (30 male, 22 female), HCQ was administered in 15 male and 12 female mice. HCQ was associated with a significant reduction of the mean (±SD) surface of the atherosclerotic plaque compared to controls (HCQ-treated vs. control, 0.04 ± 0.01 mm2 vs. 0.08 ± 0.04 mm2, p < 0.01 and 0.06 ± 0.04 mm2 vs. 0.15 ± 0.09 mm2, p = 0.012, for male and female, respectively). This reduction was associated with a significant attenuation in the mean fluorescence intensity of MPO and LC3B expression in the atherosclerotic plaque of HCQ-treated mice (p = 0.03 and p = 0.01, respectively). In line with these findings, HCQ significantly reduced the proportion of MPO+ and LC3B+ cells within the atherosclerotic lesions. HCQ administration in ApoE-/- mice may mitigate the progression of atherosclerotic plaque, by inhibiting autophagy and NET formation. Show less