Glycan in Pulmonary Medicine

Glycans are the most multiple of the four fundamental macromolecules within cells, whose diversity exceeds nucleic acids (DNA and RNA) with four nucleosides and proteins with twenty amino acids. As a seasoned technical servicer and biological products provider in the world, Creative Biolabs has gained great reputation among clients for successful projects. Nowadays, we focus long on acquired human diseases, including pulmonary medicines, based on emerging of glycobiology in order to dissect the underlying mechanism of diverse lung-related diseases.

A Synopsis in Glycans

Glycans combine dozens of monosaccharide units into branched structures and their diversity derives from linear or branched α or β linkages between monosaccharides. The biological roles of glycans span the spectrum from those that are relatively subtle, to those that are essential for the growth, development, functioning, or survival of the organism that synthesizes them. The main functions of glycans involving: the structural and modulatory properties of glycans, and the specific recognition of glycans by other molecules. Glycans constitute the most abundant form of the post-transcriptional epigenetic modifications and some studies have reported the correlation of glycans in mechanisms of nephrology.

Glycans in Chronic Obstructive Pulmonary Diseases (COPD)

COPD is a complex situation whose diagnosis requires spirometric assessment. Recently, the potential value of N-glycans as COPD biomarkers has been explored and the individual variation of plasma protein and IgG glycosylation profiles has been examined in subjects with COPD and healthy controls.

Fig.1 The abundance of plasma protein and IgG glycans in COPD subjects. (Pavić, 2018)

The results illustrated that plasma protein N-glycome in COPD exhibited impressive decrease in low branched and conversely, an increase in more complex glycan molecules, such as trisialylated, tetragalactosylated, tetrasialylated and antennary fucosylated glycoforms. There also was a significant decline observed in plasma monogalactosylated structures and the same change replicated in IgG glycome. N-glycans also displayed value in distinguishing samples in different COPD GOLD phages, where the relative abundance of more complex glycan molecules enhanced as the disease progressed. Moreover, glycans showed statistically significant connections with the frequency of exacerbations and revealed to be affected by smoking, a major risk for COPD development. This study demonstrated that complexity of glycans associates with COPD, reflecting the disease severity.

Altered Glycosylation in Pulmonary Vascular Diseases (PVD)

PVD includes pulmonary embolism, arteriovenous malformation, and pulmonary arterial hypertension. These diseases increase pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), finally leading to right ventricular hypertrophy and even heart failure. PAH has been a best-studied progressive disease, showing nitric oxide (NO) deficiency, vasoconstriction, in situ thrombosis, and intensive vascular remodeling. About other factors, dysregulated glucose metabolism may drive a rising flux into the hexosamine biosynthetic pathway. This leads to PAH patients having increased hyaluronan in the plasma, lung tissues, and pulmonary arterial smooth muscle cells. It also increases O-GlcNAc modified proteins, a process shown to regulate pulmonary arterial smooth muscle cell proliferation correlated with PAH progression, implying a potential therapeutic target.

Reference:

1. Pavić, T.; et al. N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease. J Transl Med. 2018,16(1): 323.