Myocardial infarction coincides with increased NOX2 and Nε-(carboxymethyl) lysine expression in the cerebral microvasculature

Open Heart. 2021 Nov;8(2):e001842. doi: 10.1136/openhrt-2021-001842.

Abstract

Background: Myocardial infarction (MI) is associated with mental health disorders, in which neuroinflammation and cerebral microvascular dysfunction may play a role. Previously, we have shown that the proinflammatory factors Nε-(carboxymethyl)lysine (CML) and NADPH oxidase 2 (NOX2) are increased in the human infarcted heart microvasculature. The aim of this study was to analyse the presence of CML and NOX2 in the cerebral microvasculature of patients with MI.

Methods: Brain tissue was obtained at autopsy from 24 patients with MI and nine control patients. According to their infarct age, patients with MI were divided into three groups: 3-6 hours old (phase I), 6 hours-5 days old (phase II) and 5-14 days old (phase III). CML and NOX2 in the microvasculature were studied through immunohistochemical analysis.

Results: We observed a 2.5-fold increase in cerebral microvascular CML in patients with phase II and phase III MI (phase II: 21.39±7.91, p=0.004; phase III: 24.21±10.37, p=0.0007) compared with non-MI controls (8.55±2.98). NOX2 was increased in microvessels in patients with phase II MI (p=0.002) and phase III MI (p=0.04) compared with controls. No correlation was found between CML and NOX2 (r=0.58, p=0.13).

Conclusions: MI coincides with an increased presence of CML and NOX2 in the brain microvasculature. These data point to proinflammatory alterations in the brain microvasculature that may underlie MI-associated mental health disorders.

Keywords: biomarkers; inflammation; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Cerebral Arteries / enzymology*
  • Cerebral Arteries / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Lysine / analogs & derivatives*
  • Lysine / biosynthesis
  • Male
  • Microvessels / enzymology*
  • Microvessels / pathology
  • Middle Aged
  • Myocardial Infarction / complications
  • Myocardial Infarction / enzymology*
  • Myocardial Infarction / pathology
  • NADPH Oxidase 2 / biosynthesis*
  • Neuroinflammatory Diseases / complications
  • Neuroinflammatory Diseases / enzymology*
  • Neuroinflammatory Diseases / pathology

Substances

  • Biomarkers
  • N(6)-carboxymethyllysine
  • CYBB protein, human
  • NADPH Oxidase 2
  • Lysine