ApoE and apoC-III-defined HDL subtypes: a descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity

Abstract

Background: The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods: Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m 2 , HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using nondenaturing electrophoresis and anti-apoA-I western blotting. Results: HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C-HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C-HDL relative to E-C-HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = − 0.55, P = 0.017) and E-C-alpha 1 HDL (r = − 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025).

Sodium Tanshinone IIA Sulfonate Inhibits Vascular Endothelial Cell Pyroptosis via the AMPK Signaling Pathway in Atherosclerosis

“…However, some studies have shown that other HDL-related biomarkers, such as HDL function or HDL particle number, may have more clinical significance than the relationship between HDL-C levels and cardiovascular disease. [52][53][54] Moreover, in vitro, STS inhibited mitochondrial dysfunction, NLRP3 inflammasome formation, and pyroptosis in cholesterol crystals-stimulated HUVECs. We demonstrated that STS may play a role in inflammation In this study, we observed that STS attenuated the formation of atherosclerotic lesions in WD-fed ApoE −/− mice.…”

Proteomics and lipidomics of high-density lipoprotein: Perimenopause is characterized by small triacylglycerols-enriched particles

“…The higher FC/PL, FC/CE, and TG/CE ratios especially in the largest XL-HDL particles of the PERI group indicate lower LCAT activity 38 and higher CETP activity 22 pointing towards less functional HDL. The functionality of HDL particles and the activity of LCAT and CETP are also affected by the apolipoprotein composition of the particles 39 as will be discussed together with other HDL proteomic findings.…”

“…High APOC3 levels have been linked with susceptibility to cardiovascular diseases as TG levels are positively associated with APOC3 levels 55 . An intricate interplay between APOC3 and APOE with the cholesterol efflux capacity has been observed; CETP was enriched in APOE-containing particles while LCAT was most abundant in HDL particles lacking APOC3, APOE, or both 39 .…”

Chemically‐Induced Lipoprotein Breakdown for Improved Extracellular Vesicle Purification

“…SMA pre-treatment caused a substantial reduction in ApoE (Figure 2C), which is a protein com-ponent of several types of lipoproteins. [51][52][53] Plasma processing with TFF followed by SEC showed a greater reduction in ApoE compared to TFF alone, however, the magnitude of this reduction was less than SMA pre-treatment with TFF (Figure 2C). ELISA results also indicate that SMA pre-treatment is superior to TFF alone in terms of reducing lipoprotein contaminants, such as ApoA1/high-density lipoprotein (HDL) (Figure 2D) and ApoB/LDL and VLDL (Figure 2E).…”