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ApoE and apoC-III-defined HDL subtypes: A descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity
Carlos O Mendivil
Universidad de los Andes
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5546-4206
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This work is licensed under a CC BY 4.0 License. Read Full License
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 non-denaturing 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).
Conclusions The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.
Keywords
HDL, lecithin cholesterol acyltransferase, cholesterol ester transfer protein, apolipoprotein E, apolipoprotein C-III, reverse cholesterol transport
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On 14 Apr, 2020
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Received 14 Apr, 2020
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On 13 Apr, 2020
Editor invited
On 13 Apr, 2020
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Editorial decision: Minor revision
On 26 Mar, 2020
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Received 28 Feb, 2020
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Received 28 Feb, 2020
Reviewer #3 agreed
On 17 Feb, 2020
Reviewer #2 agreed
On 31 Jan, 2020
Reviewer #1 agreed
On 16 Jan, 2020
Review #1 received
Received 16 Jan, 2020
Reviewers invited
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This preprint is under consideration at Lipids in Health and Disease. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
ApoE and apoC-III-defined HDL subtypes: A descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity
Carlos O Mendivil
Universidad de los Andes
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5546-4206
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 3
Posted 20 May, 2020
No community comments so far
Editor assigned
On 08 May, 2020
Submission checks complete
On 07 May, 2020
Editor invited
On 07 May, 2020
No comments provided
Review #3 received
Received 03 May, 2020
Editorial decision: Minor revision
On 03 May, 2020
Review #2 received
Received 27 Apr, 2020
Reviewer #3 agreed
On 21 Apr, 2020
Editor assigned
On 14 Apr, 2020
Reviewers invited
Invitations sent on 14 Apr, 2020
Reviewer #1 agreed
On 14 Apr, 2020
Reviewer #2 agreed
On 14 Apr, 2020
Review #1 received
Received 14 Apr, 2020
Submission checks complete
On 13 Apr, 2020
Editor invited
On 13 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 26 Mar, 2020
Review #3 received
Received 28 Feb, 2020
Review #2 received
Received 28 Feb, 2020
Reviewer #3 agreed
On 17 Feb, 2020
Reviewer #2 agreed
On 31 Jan, 2020
Reviewer #1 agreed
On 16 Jan, 2020
Review #1 received
Received 16 Jan, 2020
Reviewers invited
Invitations sent on 15 Jan, 2020
Editor assigned
On 06 Jan, 2020
Submission checks complete
On 05 Jan, 2020
Editor invited
On 05 Jan, 2020
First submitted
On 03 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 non-denaturing 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).
Conclusions The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5