Imaging of Intracellular and Extracellular ROS Levels in Atherosclerotic Mouse Aortas Ex Vivo: Effects of Lipid Lowering by Diet or Atorvastatin
Artikel i vetenskaplig tidskrift, 2015

Objective The first objective was to investigate if intracellular and extracellular levels of reactive oxygen species (ROS) within the mouse aorta increase before or after diet-induced lesion formation. The second objective was to investigate if intracellular and extracellular ROS correlates to cell composition in atherosclerotic lesions. The third objective was to investigate if intracellular and extracellular ROS levels within established atherosclerotic lesions can be reduced by lipid lowering by diet or atorvastatin. To address our objectives, we established a new imaging technique to visualize and quantify intracellular and extracellular ROS levels within intact mouse aortas ex vivo. Using this technique, we found that intracellular, but not extracellular, ROS levels increased prior to lesion formation in mouse aortas. Both intracellular and extracellular ROS levels were increased in advanced lesions. Intracellular ROS correlated with lesion content of macrophages. Extracellular ROS correlated with lesion content of smooth muscle cells. The high levels of ROS in advanced lesions were reduced by 5 days high dose atorvastatin treatment but not by lipid lowering by diet. Atorvastatin treatment did not affect lesion inflammation (aortic arch mRNA levels of CXCL 1, ICAM-1, MCP-1, TNF-alpha, VCAM, IL-6, and IL-1 beta) or cellular composition (smooth muscle cell, macrophage, and T-cell content). Aortic levels of intracellular ROS increase prior to lesion formation and may be important in initiation of atherosclerosis. Our results suggest that within lesions, macrophages produce mainly intracellular ROS whereas smooth muscle cells produce extracellular ROS. Short term atorvastatin treatment, but not lipid lowering by diet, decreases ROS levels within established advanced lesions; this may help explain the lesion stabilizing and anti-inflammatory effects of long term statin treatment.

Multidisciplinary Sciences

PLAQUES

VASCULAR CELLS

SUPEROXIDE ANION PRODUCTION

ATHEROGENESIS

EXPRESSION

OXIDATIVE STRESS

HYPERCHOLESTEROLEMIA

ATHERECTOMY

MICE

DYSFUNCTION

Författare

Matias Ekstrand

Göteborgs universitet

Maria Gustafsson Trajkovska

Göteborgs universitet

Jeanna Perman Sundelin

Göteborgs universitet

Per Fogelstrand

Göteborgs universitet

Martin Adiels

Göteborgs universitet

M. Johansson

Lillemor Mattsson Hultén

Göteborgs universitet

Jan Borén

Göteborgs universitet

Max Levin

Göteborgs universitet

PLoS ONE

1932-6203 (ISSN)

Vol. 10 6 Article Number: e0130898-

Ämneskategorier

Kardiologi

DOI

10.1371/journal.pone.0130898

PubMed

26098110