3.1.1 Research progress of O-Glycomics and heart disease
O-GlcNAcylation is a special sugar modification after protein
transcription and translation, which is related to a variety of
pathophysiological processes in cells[32]. The total level of
O-GlcNAcylation is determined by the regulation of mitochondrial energy
metabolism. The two key enzymes involved in this regulation process are
O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA)[33].
Some researchers have found that in infarcted heart failure, the
specific loss of OGT in cardiomyocytes will lead to a decrease in
O-GlcNAc glycosylation, increase apoptosis and fibrosis, thereby
aggravating cardiac remodeling and ultimately aggravating cardiac
dysfunction and mortality, which indicates that elevated O-GlcNAc
glycosylation may improve heart failure[34]. In addition, in
patients with diabetes or hyperglycemia and myocardial dysfunction,
studies have also found that the level of O-GlcNAc glycosylation is
increased, and OGT inhibitors can improve pathological myocardial
hypertrophy[35].
However, some studies have found that intracellular O-GlcNAcylation is
significantly increased in heart failure. This seems to mean that
O-GlcNAc glycosylation is harmful. Although increased O-GlcNAcylation is
currently one of the hallmarks of heart failure, it is not clear whether
excessive O-GlcNAcylation causes or promotes heart failure and
cardiomyopathy[36]. Excessive O-GlcNAcylation can lead to
cardiomyopathy, which may be due to the blockage of mitochondrial energy
metabolism, while increasing OGA activity and reducing O-GlcNAcylation
levels may alleviate heart failure and cardiomyopathy[37].
Increased O-GlcNAcylation in myocardium is associated with a variety of
cardiovascular and metabolic diseases, such as aortic stenosis,
hypertension, ischemia and diabetes[33, 34]. The research team led
by Mark Anderson and Priya Umapathi of Johns Hopkins University in the
United States published important research results in the top journal
Circulation in the cardiovascular field, providing a transgenic mouse
model that can independently control the level of O-GlcNAcylation in the
myocardium to clarify that O-GlcNAcylation in the myocardium may not
depend on pathological stress response. Elevated levels of
O-GlcNAcylation in the myocardium can cause dilated cardiomyopathy and
premature death, while overexpression of OGA in the myocardium can
reduce the level of O-GlcNAcylation and specifically protect
pathological cardiac hypertrophy[38].
This suggests that reducing excessive O-GlcNAcylation in myocardium may
contribute to the treatment of heart failure, and O-GlcNAcylation is
expected to become a new target for the treatment of cardiomyopathy,
which is of great significance for clinical application. Related fields
have been further explored with the efforts of Chinese scientists.
Professor Zhang Zhenlu’s team found that glycosylation is an inevitable
influencing factor for all NT-proBNP tests. The glycosylation ratio of
proBNP is as high as 70% in chronic heart failure, which makes the
detection value of NT-proBNP abnormally low, resulting in false
negatives[39]. In addition, more than 30% of patients with chronic
heart failure are clinically complicated with renal insufficiency. It
should be noted that renal insufficiency can lead to abnormal elevation
of NT-proBNP, causing false positives and interfering with clinical
judgment[33]. For these patients, BNP detection should be preferred
to obtain accurate and reliable test results (Figure 1).