title: 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.
abstract: 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.
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Mary F
authors: MF
authors: Lopez
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Bryan
authors: B
authors: Krastins
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: David A
authors: DA
authors: Sarracino
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Gregory
authors: G
authors: Byram
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Maryann S
authors: MS
authors: Vogelsang
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Amol
authors: A
authors: Prakash
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Scott
authors: S
authors: Peterman
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Shadab
authors: S
authors: Ahmad
authors: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.
authors: Gouri
authors: G
authors: Vadali
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Wenjun
authors: W
authors: Deng
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Ignacio
authors: I
authors: Inglessis
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Tom
authors: T
authors: Wickham
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Kathleen
authors: K
authors: Feeney
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: G William
authors: GW
authors: Dec
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Igor
authors: I
authors: Palacios
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Ferdinando S
authors: FS
authors: Buonanno
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: Eng H
authors: EH
authors: Lo
authors: Clinical Proteomics Research Center and Cardio-Neurology Clinic, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.
authors: MingMing
authors: M
authors: Ning
keywords: Albumin; Biomarker; Cerebrovascular disease; Discovery; Ischemic stroke; Mass spectrometry; PFO; Patent foramen ovale; Proteomics; Stroke