Higher Levels of CML and NOX2 in Brain Microvasculature Post-Myocardial Infarction

Medical illustration of a brain with stroke symptoms
Researchers sought to examine the presence of CML and NOX2 proinflammatory factors in the brain microvasculature of patients with myocardial infarction.

Increased levels of Nε-(carboxymethyl)lysine (CML) and NADPH oxidase 2 (NOX2) in the cerebral microvasculature after myocardial infarction (MI) suggest proinflammatory alterations in brain microvasculature could contribute to MI-related mental health disorders, according to research published in Open Heart.

For the study, researchers examined brain tissue collected at autopsy from 24 individuals with MI and 9 individuals in a control group, the latter of whom showed no evidence of either brain or heart disease. The brain tissue samples were grouped according to the age of the individuals’ infarct: phase I (3-6 hours old), phase II (6 hours to 5 days old), and phase III (5-14 days old). Immunohistochemical analysis was used to analyze CML and NOX2 in the brain microvasculature. An intensity scoring method was used to quantify CML staining, with a score of 1, 2, or 3 (weak, moderate, or strong positive, respectively) assigned to each CML-positive blood vessel.

Compared with controls, whose immunohistochemical CML score per cm2 was 8.55±2.98, there were significant increases in cerebral microvascular CML among individuals with both phase II (21.39±7.91; P =.004) and III (24.21±10.37; P =.0007) MI. Compared with the number of NOX2-positive blood vessels per cm2 among controls (7.65±2.44), there was significantly higher NOX2 in phase II (12.11±2.14; P =.002) and III (10.69±1.77; P =.04) MI groups. There was no significant association between CML and NOX2 (r=0.58, P =.13).

Limitations to this study included a small sample size, as well as a lack of information on the study’s individuals due to data being autopsy derived.

The study researchers concluded that “the [advanced glycation end]-product CML and the [reactive oxygen species] producer NOX2 are increased in the microvasculature of the brain after MI, which could point to MI-induced cerebrovascular dysfunction.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Korn A, Baylan U, Simsek S, et al. Myocardial infarction coincides with increased NOX2 and Nε-(carboxymethyl) lysine expression in the cerebral microvasculature. Open Heart. 2021;8:e001842. doi:10.1136/openhrt-2021-001842.