Atherosclerotic plaque inflammation varies between vascular sites and correlates with response to inhibition of lipoprotein-associated phospholipase A2

Despite systemic exposure to risk factors, the circulatory system develops varying patterns of atherosclerosis for unclear reasons. In a porcine model, we investigated the relationship between site-specific lesion development and inflammatory pathways involved in the coronary arteries (CORs) and dis...

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Bibliographic Details
Published in:Journal of the American Heart Association 2015-02, Vol.4 (2)
Main Authors: Fenning, Robert S, Burgert, Mark E, Hamamdzic, Damir, Peyster, Eliot G, Mohler, Emile R, Kangovi, Shreya, Jucker, Beat M, Lenhard, Stephen C, Macphee, Colin H, Wilensky, Robert L
Format: Article
Language:English
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase - antagonists & inhibitors
Animals
Aorta, Abdominal - immunology
Aorta, Abdominal - pathology
Atherosclerosis - metabolism
Benzaldehydes - pharmacology
Coronary Vessels - immunology
Coronary Vessels - pathology
Diabetes Mellitus - immunology
Diabetes Mellitus - pathology
Disease Models, Animal
Gene Expression - drug effects
Hypercholesterolemia - immunology
Hypercholesterolemia - pathology
Inflammation - metabolism
Macrophages - immunology
Male
Original Research
Oximes - pharmacology
Phospholipase A2 Inhibitors - pharmacology
Plaque, Atherosclerotic - metabolism
Plaque, Atherosclerotic - pathology
Swine
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Summary:Despite systemic exposure to risk factors, the circulatory system develops varying patterns of atherosclerosis for unclear reasons. In a porcine model, we investigated the relationship between site-specific lesion development and inflammatory pathways involved in the coronary arteries (CORs) and distal abdominal aortas (AAs). Diabetes mellitus (DM) and hypercholesterolemia (HC) were induced in 37 pigs with 3 healthy controls. Site-specific plaque development was studied by comparing plaque severity, macrophage infiltration, and inflammatory gene expression between CORs and AAs of 17 DM/HC pigs. To assess the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in plaque development, 20 DM/HC pigs were treated with the Lp-PLA2 inhibitor darapladib and compared with the 17 DM/HC untreated pigs. DM/HC caused site-specific differences in plaque severity. In the AAs, normalized plaque area was 4.4-fold higher (P
ISSN:2047-9980
DOI:10.1161/JAHA.114.001477