Identification of haptoglobin and apolipoprotein A-I as biomarkers for high altitude pulmonary edema

Abstract

We have investigated the plasma proteome using 2D gel electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight from patients with high altitude pulmonary edema (HAPE). A complete proteomic analysis was performed on 20 patients with HAPE and ten healthy sea level controls. In total, we have identified 25 protein spots in human plasma and found that 14 of them showed altered changes in HAPE patients, which mainly were acute phase proteins (APPs), compliment components, and apolipoproteins among others. Among the APPs, haptoglobin α2 chain, haptoglobin β chain, transthyretin, and plasma retinol binding precursor showed overexpression in HAPE patients as compared to controls. To validate the result of proteomic analysis, two proteins were selected for enzyme-linked immunosorbent assay and Western blotting analysis. Our data conclusively shows that two proteins, haptoglobin and apolipoprotein A-I are upregulated in plasma of HAPE patients. These proteins may provide a fast and effective control of inflammatory damage until the subsequent mechanisms can begin to operate. Taken together, our findings further support the hypothesis that inflammatory response system is linked to the pathophysiology of HAPE.

Proteomic analysis of changes in protein expression in serum from animals exposed to paraquat

“…Karthik et al (21) demonstrated that the expression of an Hp precursor, Pphg, was greatly altered in the alloxan-induced diabetes model. In addition, the expression of Pphg and Hp in patient urine was dramatically increased in the presence of passive Heymann nephritis and suggested that Pphg and Hp are appropriate candidates for therapeutic targeting and potentially novel biomarkers in membranous nephropathy (MN) and high altitude pulmonary edema (22,23). We identified Pphg via proteomic analysis and observed that its expression was dramatically induced in PQ-treated rat serum.…”

High Altitude Pulmonary Edema: An Update on Omics Data and Redefining Susceptibility

“…Yan and coworkers suggested that proteins of the acute phase response in HAPE patients can potentially be used as biomarkers in future [52]. Furthermore, another study from our lab had indicated the increased levels of transthrytin in high altitude natives in comparison to lowlanders, which suggest the role of this protein in adaptability to high altitude [49] These results suggest the possible role of pathways directly associated with lipid transport and its metabolism and vasculature remodeling. However a connecting link between these changes is missing and more studies involving systems biology approach in HAPE and their integration could provide a better picture.…”

“…Plasma proteomics studies carried out at the author's lab showed that during acute phase, haptoglobin, and apolipoprotein A-I were found to be overexpressed in HAPE patients compared to sea level residents [49]. During the recovery phase, apolipoprotein A-IV and serum amyloid P component was observed to be overexpressed [49,52].…”

“…Some independent proteomics studies on HAPE susceptibility that were carried by Yasmin et al [49] were primarily from the HAPE patients but non-availability of samples from healthy, mountain-travelers and their travel record posed a difficulty in profiling susceptibility of HAPE. However some of the undermentioned proteins have emerged as putative biomarkers.…”

“…During the recovery phase, apolipoprotein A-IV and serum amyloid P component was observed to be overexpressed [49,52]. Yan and coworkers suggested that proteins of the acute phase response in HAPE patients can potentially be used as biomarkers in future [52].…”