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Regulation of Endogenous Apolipoprotein E Secretion by Macrophages

Kockx, Maaike, Jessup, Wendy, Kritharides, Leonard·2008·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.108.164350
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Abstract

Apolipoprotein E has critical roles in the protection against atherosclerosis and is understood to follow the classical constitutive secretion pathway. Recent studies have indicated that the secretion of apoE from macrophages is a regulated process of unexpected complexity. Cholesterol acceptors such as apolipoprotein A-I, high density lipoprotein, and phospholipid vesicles can stimulate apoE secretion. The ATP binding cassette transporter ABCA1 is involved in basal apoE secretion and in lipidating apoE-containing particles secreted by macrophages. However, the stimulation of apoE secretion by apoA-I is ABCA1-independent, indicating the existence of both ABCA1-dependent and -independent pathways of apoE secretion. The release of apoE under basal conditions is also regulated, requiring intact protein kinase A activity, intracellular calcium, and an intact microtubular network. Mathematical modeling of apoE turnover indicates that whereas some pools of apoE are committed to either secretion or degradation, other pools can be diverted from degradation toward secretion. Targeted inhibition or stimulation of specific apoE trafficking pathways will provide unique opportunities to regulate the biology of this important molecule.

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  • ApoE is secreted through the classical secretory pathway whereby it is produced in the endoplasmic reticulum, transits to the golgi and trans-golgi, and then is transported to the plasma membrane.

    “ApoE is secreted through the classical secretory pathway whereby it is produced in the endoplasmic reticulum (Fig. 1A), transits to the golgi and trans-golgi (Fig. 1B), and then is transported to the plasma membrane [21].”

    From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [21]

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Metadata

Authors
Kockx, M., Jessup, W., & Kritharides, L.
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008-06
Volume
28
Issue
6
Pages
1060-1067
ISSN
  • 1079-5642
  • 1524-4636
DOI
10.1161/atvbaha.108.164350
Cited by
84
References
1
Language
en

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