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

• Published in: Scientific reports Vol. 8; no. 1; pp. 15078 - 13
• Main Authors: Rinne, Petteri, Lyytikäinen, Leo-Pekka, Raitoharju, Emma, Kadiri, James J, Kholova, Ivana, Kähönen, Mika, Lehtimäki, Terho, Oksala, Niku
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 10.10.2018; Nature Publishing Group UK
• Subjects: ABCA1 protein; Arteriosclerosis; Atherosclerosis; ATP-binding protein; Bioavailability; Carboxypeptidase E; Cardiovascular disease; Cholesterol; Coronary artery; DNA microarrays; Enzymes; Femur; Fish; Heart diseases; Inflammation; Leukocytes; Localization; Lysosomal Pro-X carboxypeptidase; Macrophages; Melanocyte-stimulating hormone; Plaques; Proopiomelanocortin; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-33523-7

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) 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. α-MSH-producing enzyme, carboxypeptidase E, was down-regulated, whereas prolylcarboxypeptidase, an enzyme inactivating α-MSH, was up-regulated in unstable plaques compared to stable plaques, suggesting a possible reduction in intraplaque α-MSH levels. Second, immunohistochemical analyses revealed the presence of α-MSH in atherosclerotic plaques and its localization in macrophages and other cell types. Lastly, supporting the role of α-MSH in reverse cholesterol transport, POMC expression correlated with ABCA1 and ABCG1 in human plaque and whole blood samples. In conclusion, α-MSH is expressed in atherosclerotic plaques and its processing enzymes associate with plaque stability, suggesting that measures to enhance the local bioavailability of α-MSH might protect against atherosclerosis.