A1 Refereed original research article in a scientific journal
Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis -Tampere Vascular Study
Authors: Petteri Rinne, Leo-Pekka Lyytikäinen, Emma Raitoharju, James J. Kadiri, Ivana Kholova, Mika Kähönen, Terho Lehtimäki, Niku Oksala
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 15078
Volume: 8
Number of pages: 13
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-018-33523-7
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/36455497
alpha-melanocyte-stimulating hormone (alpha-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. alpha-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and alpha-MSH expression in atherosclerosis. First, transcript levels of POMC and its processing enzymes were analyzed in human arterial plaques (n = 68) and non-atherosclerotic controls (n = 24) as well as in whole blood samples from coronary artery disease patients (n = 55) and controls (n = 45) by microarray. POMC expression was increased in femoral plaques compared to control samples as well as in unstable advanced plaques. alpha-MSH-producing enzyme, carboxypeptidase E, was down-regulated, whereas prolylcarboxypeptidase, an enzyme inactivating alpha-MSH, was up-regulated in unstable plaques compared to stable plaques, suggesting a possible reduction in intraplaque alpha-MSH levels. Second, immunohistochemical analyses revealed the presence of alpha-MSH in atherosclerotic plaques and its localization in macrophages and other cell types. Lastly, supporting the role of alpha-MSH in reverse cholesterol transport, POMC expression correlated with ABCA1 and ABCG1 in human plaque and whole blood samples. In conclusion, alpha-MSH is expressed in atherosclerotic plaques and its processing enzymes associate with plaque stability, suggesting that measures to enhance the local bioavailability of alpha-MSH might protect against atherosclerosis.
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