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Fig. 3. Shedding of excess LDLR in PCSK9-deficient mice depends on estrogen and is achieved by metalloproteases. (A) Plasma levels of shed LDLR (sLDLR) were assessed in all mouse models and normalized to WT male levels. n = 4–5 mice. (B) sLDLR was measured for 28 h in WT and KO male mice after vehicle (Veh) or <t>E2</t> injection (50 μg/kg; n = 4–6 mice). (C) WT and KO female mice received an intraperitoneal injection of vehicle or <t>the</t> <t>metalloprotease</t> inhibitor BB-94 (12.5 mg/kg; n = 4–5 mice). Mean ± SEM were normalized to WT Veh value at t = 0 and set to 1. P values were determined using Mann-Whitney U test (A; non parametric data) and 2-way ANOVA followed by Tukey’s multiple comparisons test (B and C).
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Fig. 3. Shedding of excess LDLR in PCSK9-deficient mice depends on estrogen and is achieved by metalloproteases. (A) Plasma levels of shed LDLR (sLDLR) were assessed in all mouse models and normalized to WT male levels. n = 4–5 mice. (B) sLDLR was measured for 28 h in WT and KO male mice after vehicle (Veh) or E2 injection (50 μg/kg; n = 4–6 mice). (C) WT and KO female mice received an intraperitoneal injection of vehicle or the metalloprotease inhibitor BB-94 (12.5 mg/kg; n = 4–5 mice). Mean ± SEM were normalized to WT Veh value at t = 0 and set to 1. P values were determined using Mann-Whitney U test (A; non parametric data) and 2-way ANOVA followed by Tukey’s multiple comparisons test (B and C).

Journal: Biochimica et biophysica acta. Molecular and cell biology of lipids

Article Title: PCSK9 deficiency results in a specific shedding of excess LDLR in female mice only: Role of hepatic cholesterol.

doi: 10.1016/j.bbalip.2022.159217

Figure Lengend Snippet: Fig. 3. Shedding of excess LDLR in PCSK9-deficient mice depends on estrogen and is achieved by metalloproteases. (A) Plasma levels of shed LDLR (sLDLR) were assessed in all mouse models and normalized to WT male levels. n = 4–5 mice. (B) sLDLR was measured for 28 h in WT and KO male mice after vehicle (Veh) or E2 injection (50 μg/kg; n = 4–6 mice). (C) WT and KO female mice received an intraperitoneal injection of vehicle or the metalloprotease inhibitor BB-94 (12.5 mg/kg; n = 4–5 mice). Mean ± SEM were normalized to WT Veh value at t = 0 and set to 1. P values were determined using Mann-Whitney U test (A; non parametric data) and 2-way ANOVA followed by Tukey’s multiple comparisons test (B and C).

Article Snippet: Male mice were treated with E2 (see above) and male or female mice were treated with the metalloprotease inhibitors BB-94 and ZLDI-8 resuspended in DMSO (MedChemExpress, Princeton, NJ) and diluted ≥10-fold in corn oil before intraperitoneal injection.

Techniques: Clinical Proteomics, Injection, MANN-WHITNEY