Proteomic signatures of serum albumin-bound proteins from stroke patients with and without endovascular closure of PFO are significantly different and suggest a novel mechanism for cholesterol efflux

Clinical Proteomics

MingMing Ning¹  Eng H Lo¹  Ferdinando S Buonanno¹  Igor Palacios¹  G William Dec¹  Kathleen Feeney¹  Tom Wickham¹  Ignacio Inglessis¹  Wenjun Deng¹  Gouri Vadali²  Shadab Ahmad²  Scott Peterman²  Amol Prakash²  Maryann S Vogelsang²  Gregory Byram²  David A Sarracino²  Bryan Krastins²  Mary F Lopez² 

[1] Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139, UK

关键词: Albumin;    Proteomics;    Mass spectrometry;    PFO;    Patent foramen ovale;    Ischemic stroke;    Cerebrovascular disease;    Stroke;    Discovery;    Biomarker;   

Others  :  1092783
DOI  :  10.1186/1559-0275-12-2

 received in 2014-10-23, accepted in 2014-12-23,  发布年份 2015

【 摘 要 】

Background

The anatomy of PFO suggests that it can allow thrombi and potentially harmful circulatory factors to travel directly from the venous to the arterial circulation – altering circulatory phenotype. Our previous publication using high-resolution LC-MS/MS to profile protein and peptide expression patterns in plasma showed that albumin was relatively increased in donor samples from PFO-related than other types of ischemic strokes. Since albumin binds a host of molecules and acts as a carrier for lipoproteins, small molecules and drugs, we decided to investigate the albumin-bound proteins (in a similar sample cohort) in an effort to unravel biological changes and potentially discover biomarkers related to PFO-related stroke and PFO endovascular closure.

Methods

The method used in this study combined albumin immuno-enrichment with high resolution LC-MS in order to specifically capture and quantify the albumin-bound proteins. Subsequently, we measured cholesterol and HDL in a larger, separate cohort of PFO stroke patients, pre and post closure.

Results

The results demonstrated that a number of proteins were specifically associated with albumin in samples with and without endovascular closure of the PFO, and that the protein profiles were very different. Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant. Pathway analysis of the MS results suggested that enhanced cholesterol efflux and reduced lipid oxidation were associated with PFO closure. Measurement of total cholesterol and HDL in a larger cohort of PFO closure samples using a colorimetric assay was consistent with the proteomic predictions.

Conclusions

The collective data presented in this study demonstrate that analysis of albumin-bound proteins could provide a valuable tool for biomarker discovery on the effects of PFO endovascular closure. In addition, the results suggest that PFO endovascular closure can potentially have effects on HDL, cholesterol and albumin-bound ApoA-I abundance, therefore possibly providing benefits in cardioprotective functions.

【 授权许可】

   
2015 Lopez et al.; licensee BioMed Central.

【 图 表 】

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