• John Tengbom, Sofia Cederström, Dinos Verouhis, Felix Böhm, Per Eriksson, Lasse Folkersen, Anders Gabrielsen, Tomas Jernberg, Pia Lundman, Jonas Persson, Nawzad Saleh, Magnus Settergren, Peder Sörensson, Yahor Tratsiakovich, Per Tornvall, Christian Jung, and John Pernow.
• Unit of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
• J. Intern. Med. 2021 Nov 1; 290 (5): 1061-1070.

BackgroundThe mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unresolved. Increased arginase 1 activity leads to reduced nitric oxide (NO) production and increased formation of reactive oxygen species due to uncoupling of the NO-producing enzyme endothelial NO synthase (eNOS). This contributes to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction.ObjectiveThe purpose of this study was to test the hypothesis that arginase gene and protein expression are upregulated in patients with STEMI.MethodsTwo cohorts of patients with STEMI were included. In the first cohort (n = 51), expression of arginase and NO-synthases as well as arginase 1 protein levels were determined and compared to a healthy control group (n = 45). In a second cohort (n = 68), plasma arginase 1 levels and infarct size were determined using cardiac magnetic resonance imaging.ResultsExpression of the gene encoding arginase 1 was significantly elevated at admission and 24-48 h after STEMI but not 3 months post STEMI, in comparison with the control group. Expression of the genes encoding arginase 2 and endothelial NO synthase (NOS3) were unaltered. Arginase 1 protein levels were elevated at admission, 24 h post STEMI and remained elevated for up to 6 months. No significant correlation between plasma arginase 1 protein levels and infarct size was observed.ConclusionThe markedly increased gene and protein expression of arginase 1 already at admission indicates a role of arginase 1 in the development of STEMI.© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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