Plasma Proteomic Study in Pulmonary Arterial Hypertension Associated with Congenital Heart Diseases

Abstract

Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) has serious consequence and plasma protein profiles in CHD-PAH are unknown. We aimed to reveal the differential plasma proteins in 272 CHD patients with or without PAH. Various types of CHD-PAH were studied. Differential plasma proteins were first detected by iTRAQ proteomic technology and those with significant clinical relevance were selected for further ELISA validation in new cohort of patients. Among the 190 differential plasma proteins detected by iTRAQ, carbamoyl-phosphate synthetase I (CPSI, related to urea cycle and endogenous nitric oxide production) and complement factor H-related protein 2 (CFHR2, related to complement system and coagulant mechanism) were selected for further ELISA validation in new cohort of 152 patients. Both CPSI and CFHR2 were down-regulated with decreased plasma levels (p < 0.01). Thus, we for the first time in CHD-PAH patients identified a large number of differential plasma proteins. The decreased CPSI expression in CHD-PAH patients may reveal a mechanism related to endogenous nitric oxide and the decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism. The findings may open a new direction for translational medicine in CHD-PAH with regard to the diagnosis and progress of the disease.

Remote Sensing Between Liver and Intestine: Importance of Microbial Metabolites

“…Gut microbiota promotes an increase in insulin-like growth factor 1 (IGF-1), which is known to promote bone growth (102). Colonization of GF mice with gut microbiota from CV mice increases serum IGF-1, which is produced by liver and adipose tissue (102).…”

“…Colonization of GF mice with gut microbiota from CV mice increases serum IGF-1, which is produced by liver and adipose tissue (102). In addition, SCFA supplementation also leads to an increase in serum IGF-1 levels (103).…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…The Polysulfoethyl columns from Poly‐LC (Neste group) have been by far the most widely used column type. Notable examples where SCX fractionation has been used include the study by Juhasz et al where it was used in combination with tandem depletion and LC‐MALDI, reporting 470 proteins detected in nine iTRAQ experiments, the ESI study of gastric adenocarcinoma by Subbannayya et al where they reported identification 643 proteins, and the ESI & MALDI study of Zhang et al where they reported 1044 proteins . SCX fractionation has mostly been performed off‐line, necessitating additional concentration and desalting steps.…”

“…Zhang et al investigated pulmonary arterial hypertension in relation to congenital heart diseases in a group of 140 children (3–11 years) with heart defects . Detection and quantification of in the order of 1000 proteins were reported, 338 of which were detected with two or more unique peptides.…”

Application of iTRAQ-Based Quantitative Proteomics Approach to Identify Deregulated Proteins Associated with Liver Toxicity Induced by Polygonum Multiflorum in Rats

“…The proteins were considered to be differentially expressed if the iTRAQ ratio was >1.2 or<0.833. This cut-off value is recommended in the literature [5, 6] and was used to obtain more comprehensive information regarding the differences in the proteomic analysis.…”