Triglyceride-rich HDL3 from patients with familial hypercholesterolemia are less able to inhibit cytokine release or to promote cholesterol efflux

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Abstract

Familial hypercholesterolemia (FH) is associated with heterogeneity of the onset and severity of coronary heart disease (CHD). In this study, we investigated different low-grade proinflammatory markers and the atheroprotective function of the HDL3 subfraction in FH-patients (n = 13) with identical LDL-receptor mutations and in age- and sex-matched healthy controls (n = 11). Compared with healthy controls, FH-patients had greater gene expressions of the proatherogenic mediators TNF-a and IL-8 in circulating peripheral blood mononuclear cells. In addition, they had a higher serum concentration of intercellular adhesion molecule-1 (ICAM-1) and a lower net antioxidant capacity. FH-derived HDL3 with a high level of triglycerides had a reduced capacity to inhibit the release of IL-8 from TNF-α-stimulated human umbilical vein endothelial cells (HUVEC) [1.864 mg/L (1.461-2.208 mg/L) vs. 1.466 mg/L (1.225-1.643 mg/L); P < 0.05; median (range)], and a reduced capacity to promote cholesterol efflux from lipid-loaded macrophages [12% (12-14%) vs. 15% (14-18%); P < 0.05; median (range)] compared with HDL3 with a lower triglyceride content. Notably, the degree of inhibition of IL-8 release from HUVEC by HDL3 was correlated with the ability of HDL3 to promote cholesterol efflux (r = -0.80, P = 0.03). In conclusion, compared with healthy controls, FH-patients are characterized by higher levels of low-grade proinflammatory markers, and FH-derived HDL3 with high triglyceride content may be more proatherogenic. These triglyceride rich-HDL3 might be partly responsible for the phenotypic variation among FH-patients with identical LDL-receptor mutations. © 2006 American Society for Nutrition.

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APA

Ottestad, I. O., Halvorsen, B., Balstad, T. R., Otterdal, K., Borge, G. I., Brosstad, F., … Holven, K. B. (2006). Triglyceride-rich HDL3 from patients with familial hypercholesterolemia are less able to inhibit cytokine release or to promote cholesterol efflux. Journal of Nutrition, 136(4), 877–881. https://doi.org/10.1093/jn/136.4.877

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