Atherosclerosis regulation via media lipid-driven VSMC cholesterol efflux switch.

Abstract:

:It is known, that initial events in atherosclerosis arise in the intima with a parallel influx of inflammatory cells. I propose the opposite - that the disease onset begins from the media vascular smooth muscle cell (VSMC) involvement and through its utilization of modified low-density lipoproteins (LDL), and free or esterified cholesterol. Other oxidized lipoprotein molecules remain in the media which are non-removed by high-density lipoproteins (HDL), owing to their structural damages after local vasa vasorum and adventitia lymphatic disorders. Mechanism by which VSMC ingulf and degrade them includes lipid-driven activation of VSMC reverse cholesterol transport pathways from the media to macrophages, and from the last - to plasma HDL (non-damaged) and apoA-1 or - directly to them. When some of the pathways are impaired, its demands a reprogramming of the existing cholesterol removal route to another, or selective gene involvements and transcriptional regulation of inflammatory signaling. Intima cell call-effects may be linked after their down-regulation with the expression of cytokines, chemokines by migrating VSMC to stem cells for dose-dependent proliferation, VSMC and macrophage maturation in non- and inflammatory phases of early or late atherosclerosis.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

Chepelenko GV

doi

10.1016/j.mehy.2014.12.002

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

141-4

issue

2

eissn

0306-9877

issn

1532-2777

pii

S0306-9877(14)00437-X

journal_volume

84

pub_type

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