The phenomenon of atherosclerosis reversal and regression : lessons from animal models

Dimitry A. Chistiakov, Veronika A. Myasoedova, Victor V. Revin, Alexander N. Orekhov, Yuri V. Bobryshev

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Studies in non-rodent and murine models showed that atherosclerosis can be reversed. Atherosclerosis progression induced by high-fat or cholesterol-rich diet can be reduced and reversed to plaque regression after switching to a normal diet or through administration of lipid-lowering agents. The similar process should exist in humans after implementation of lipid-lowering therapy and as a result of targeting of small rupture-prone plaques that are major contributors for acute atherosclerotic complications. Lowering of low density lipoprotein (LDL) cholesterol and the activation of reverse cholesterol transport lead to a decline in foam cell content, to the depletion of plaque lipid reservoirs, a decrease in lesional macrophage numbers through the activation of macrophage emigration and, probably, apoptosis, dampening plaque inflammation, and the induction of anti-inflammatory macrophages involved in clearance of the necrotic core and plaque healing. By contrast, plaque regression is characterized by opposite events, leading to the retention of atherogenic LDL and oxidized LDL particles in the plaque, an increased flux of monocytes, the immobilization of macrophages in the intimal vascular tissues, and the propagation of intraplaque inflammation. Transfer of various apolipoprotein (apo) genes to spontaneously hypercholesterolemic mice deficient for either apoE or LDL receptor and, especially, the implementation of the transplantation murine model allowed studying molecular mechanisms of atherosclerotic regression, associated with the depletion of atherogenic lipids in the plaque, egress of macrophages and phenotypic switch of macrophages from the proinflammatory M1 to the anti-inflammatory M2.
Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalExperimental and Molecular Pathology
Volume102
Issue number1
DOIs
Publication statusPublished - 2017

Keywords

  • atherosclerosis
  • cholesterol
  • macrophages

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