Arginase 1 is upregulated at admission in patients with ST-elevation myocardial infarction

J Intern Med. 2021 Nov;290(5):1061-1070. doi: 10.1111/joim.13358. Epub 2021 Aug 23.

Abstract

Background: The 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.

Objective: The purpose of this study was to test the hypothesis that arginase gene and protein expression are upregulated in patients with STEMI.

Methods: Two 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.

Results: Expression 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.

Conclusion: The markedly increased gene and protein expression of arginase 1 already at admission indicates a role of arginase 1 in the development of STEMI.

Keywords: ST-elevation myocardial infarction; arginase; cardiac magnetic resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginase* / blood
  • Arginase* / genetics
  • Humans
  • Myocardial Reperfusion Injury* / genetics
  • Nitric Oxide Synthase Type III
  • ST Elevation Myocardial Infarction* / genetics
  • Treatment Outcome

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Arginase