Jing Liu (China)
Xiangya Hospital Department of Cardiovascular SurgeryAuthor Of 1 Presentation
O027 - Excess HDL Free Cholesterol Bioavailability Drives Free Cholesterol Accretion into Macrophages and Erythrocytes in SCRAB1-/- mice. (ID 1023)
Abstract
Background and Aims
Aim: In humans, very high plasma HDL-cholesterol concentrations are associated with increased all cause- and atherosclerotic cardiovascular disease (ASCVD)-associated death. The HDL receptor-deficient mouse (Scarb1-/-), a robust model of this phenotype, is characterized by high free cholesterol (FC) bioavailability due to too many HDL particles that are FC-rich. Clinically, plasma LDL and HDL are quantified according to their total cholesterol content, the sum of FC and esterified cholesterol, which likely contribute to ASCVD pathophysiology differently. A Western diet induces ASCVD in Scarb1-/- mice, despite an attendant increase in HDL, the so-called “good cholesterol.” We tested the hypothesis that high HDL-FC bioavailability contributes to ASCVD in Scarb1-/- mice by increasing FC flux into macrophage cells and erythrocytes.
Methods
Methods: Influx of HDL-FC and efflux of macrophage FC were determined between WT and SCARB1-/- HDL and J774 macrophage cells. HDL of both genotypes were radiolabelled with [3H]FC, injected into autologous mice, and the rates of plasma clearance and erythrocyte uptake were determined.
Results
Results: Compared to WT mice, in Scarb1-/- mice, autologous HDL-FC cleared faster and more HDL-FC transferred to macrophages. The FC/phospholipid ratios of HDL, LDL, erythrocytes, as well as some tissues, were higher. The high FC/phospholipid ratios of ovaries, erythrocytes, heart, and macrophages in response to the higher HDL-FC bioavailability in Scarb1-/- mice is associated respectively with female infertility, impaired cell maturation, cardiac dysfunction, and ASCVD.
Conclusions
Conclusion: These findings provide a rationale for human studies to determine the utility of HDL-FC bioavailability as a risk factor for ASCVD and other pathologies.
Presenter of 1 Presentation
O027 - Excess HDL Free Cholesterol Bioavailability Drives Free Cholesterol Accretion into Macrophages and Erythrocytes in SCRAB1-/- mice. (ID 1023)
Abstract
Background and Aims
Aim: In humans, very high plasma HDL-cholesterol concentrations are associated with increased all cause- and atherosclerotic cardiovascular disease (ASCVD)-associated death. The HDL receptor-deficient mouse (Scarb1-/-), a robust model of this phenotype, is characterized by high free cholesterol (FC) bioavailability due to too many HDL particles that are FC-rich. Clinically, plasma LDL and HDL are quantified according to their total cholesterol content, the sum of FC and esterified cholesterol, which likely contribute to ASCVD pathophysiology differently. A Western diet induces ASCVD in Scarb1-/- mice, despite an attendant increase in HDL, the so-called “good cholesterol.” We tested the hypothesis that high HDL-FC bioavailability contributes to ASCVD in Scarb1-/- mice by increasing FC flux into macrophage cells and erythrocytes.
Methods
Methods: Influx of HDL-FC and efflux of macrophage FC were determined between WT and SCARB1-/- HDL and J774 macrophage cells. HDL of both genotypes were radiolabelled with [3H]FC, injected into autologous mice, and the rates of plasma clearance and erythrocyte uptake were determined.
Results
Results: Compared to WT mice, in Scarb1-/- mice, autologous HDL-FC cleared faster and more HDL-FC transferred to macrophages. The FC/phospholipid ratios of HDL, LDL, erythrocytes, as well as some tissues, were higher. The high FC/phospholipid ratios of ovaries, erythrocytes, heart, and macrophages in response to the higher HDL-FC bioavailability in Scarb1-/- mice is associated respectively with female infertility, impaired cell maturation, cardiac dysfunction, and ASCVD.
Conclusions
Conclusion: These findings provide a rationale for human studies to determine the utility of HDL-FC bioavailability as a risk factor for ASCVD and other pathologies.