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Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.

ABSTRACT: ?-melanocyte-stimulating hormone (?-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. ?-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and ?-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. ?-MSH-producing enzyme, carboxypeptidase E, was down-regulated, whereas prolylcarboxypeptidase, an enzyme inactivating ?-MSH, was up-regulated in unstable plaques compared to stable plaques, suggesting a possible reduction in intraplaque ?-MSH levels. Second, immunohistochemical analyses revealed the presence of ?-MSH in atherosclerotic plaques and its localization in macrophages and other cell types. Lastly, supporting the role of ?-MSH in reverse cholesterol transport, POMC expression correlated with ABCA1 and ABCG1 in human plaque and whole blood samples. In conclusion, ?-MSH is expressed in atherosclerotic plaques and its processing enzymes associate with plaque stability, suggesting that measures to enhance the local bioavailability of ?-MSH might protect against atherosclerosis.

SUBMITTER: Rinne P

PROVIDER: S-EPMC6180013 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.

Rinne Petteri P Lyytikäinen Leo-Pekka LP Raitoharju Emma E Kadiri James J JJ Kholova Ivana I Kähönen Mika M Lehtimäki Terho T Oksala Niku N

Scientific reports 20181010 1

α-melanocyte-stimulating hormone (α-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. α-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and α-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) ...[more]

PMID: 30305673

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Dataset Information

Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.

Publications

Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.

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