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Statins Promote Cardiac Infarct Healing by Modulating Endothelial Barrier Function Revealed by Contrast-Enhanced Magnetic Resonance Imaging.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2018 Jan; Vol. 38 (1), pp. 186-194. Date of Electronic Publication: 2017 Nov 16. - Publication Year :
- 2018
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Abstract
- Objective: The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI).<br />Approach and Results: Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE <superscript>-/-</superscript> , and statin-treated ApoE <superscript>-/-</superscript> mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE <superscript>-/-</superscript> infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE <superscript>-/-</superscript> infarcts, indicated by reduced permeability. The infarcted tissue of ApoE <superscript>-/-</superscript> mice 3 days post-MI displayed an unbalanced Vegfa (vascular endothelial growth factor A)/ Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45 <superscript>+</superscript> leukocytes and inflammatory LY6C <superscript>hi</superscript> monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE <superscript>-/-</superscript> mice.<br />Conclusions: Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.<br /> (© 2017 American Heart Association, Inc.)
- Subjects :
- Angiopoietin-1 metabolism
Animals
Chemotaxis, Leukocyte drug effects
Coronary Vessels metabolism
Coronary Vessels pathology
Disease Models, Animal
Endothelium, Vascular metabolism
Endothelium, Vascular pathology
Inflammation Mediators metabolism
Leukocytes drug effects
Leukocytes metabolism
Mice, Inbred C57BL
Mice, Knockout, ApoE
Myocardial Infarction metabolism
Myocardial Infarction pathology
Predictive Value of Tests
Time Factors
Vascular Endothelial Growth Factor A metabolism
Ventricular Function, Left drug effects
Ventricular Remodeling drug effects
Capillary Permeability drug effects
Contrast Media administration & dosage
Coronary Vessels diagnostic imaging
Coronary Vessels drug effects
Endothelium, Vascular diagnostic imaging
Endothelium, Vascular drug effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Magnetic Resonance Imaging
Myocardial Infarction diagnostic imaging
Myocardial Infarction drug therapy
Wound Healing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 38
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 29146749
- Full Text :
- https://doi.org/10.1161/ATVBAHA.117.310339