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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.

Lopez MF, Krastins B, Sarracino DA, Byram G, Vogelsang MS, Prakash A, Peterman S, Ahmad S, Vadali G, Deng W, Inglessis I, Wickham T, Feeney K, Dec GW, Palacios I, Buonanno FS, Lo EH, Ning M - Clin Proteomics (2015)

Bottom Line: 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.Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant.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.

View Article: PubMed Central - PubMed

Affiliation: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.

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.

No MeSH data available.


Related in: MedlinePlus

Distribution of albumin-bound proteins in PFO closurevsno-closure sample sets. Specificity for albumin-binding was assumed when binding to the negative control (anti-BL Ab) was less than binding to the anti-albumin Ab (ratio <0.5). Eight proteins were present in both sample sets and their abundance ratios and ROC AUC scores are given in Table 3. All 8 proteins present in both sample sets have been previously identified in HDL (26).
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Fig2: Distribution of albumin-bound proteins in PFO closurevsno-closure sample sets. Specificity for albumin-binding was assumed when binding to the negative control (anti-BL Ab) was less than binding to the anti-albumin Ab (ratio <0.5). Eight proteins were present in both sample sets and their abundance ratios and ROC AUC scores are given in Table 3. All 8 proteins present in both sample sets have been previously identified in HDL (26).

Mentions: Additional file 4 lists all the albumin-bound proteins and abundance ratios in PFO closure and no-closure samples. A total of 46 albumin-bound proteins were detected in PFO closure samples, 15 with an increased ratio (>1.2) and 13 with a decreased ratio (<0.8). Forty albumin-bound proteins were detected in the PFO no-closure samples, 9 with an increased ratio (>1.2) and 19 with a decreased ratio (<0.8). Eight proteins were present in both sample sets (Figure 2), and their abundance ratios and ROC AUC scores are given in Table 3. All 8 proteins present in both sample sets have been previously identified in HDL [26]. The ROC AUC scores and abundance ratios of the 8 proteins in common were very different between the PFO closure and no closure sample groups. ApoA-1 and ApoC-III had the highest ROC AUC scores in the closure group indicating good to excellent classification power between the baseline and 3–12 month follow up samples, indicating a significant difference. Abundance ratios (baseline/follow up) for these proteins were also higher in the PFO closure sample set than in the no closure sample set, with the ApoC-III B/FU abundance ratio almost 2× higher in the closure sample group. In the no closure group, kininogen had the most significant ROC AUC score and its abundance ratio was ca 1.6× higher than in the closure group.Figure 2


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.

Lopez MF, Krastins B, Sarracino DA, Byram G, Vogelsang MS, Prakash A, Peterman S, Ahmad S, Vadali G, Deng W, Inglessis I, Wickham T, Feeney K, Dec GW, Palacios I, Buonanno FS, Lo EH, Ning M - Clin Proteomics (2015)

Distribution of albumin-bound proteins in PFO closurevsno-closure sample sets. Specificity for albumin-binding was assumed when binding to the negative control (anti-BL Ab) was less than binding to the anti-albumin Ab (ratio <0.5). Eight proteins were present in both sample sets and their abundance ratios and ROC AUC scores are given in Table 3. All 8 proteins present in both sample sets have been previously identified in HDL (26).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4305391&req=5

Fig2: Distribution of albumin-bound proteins in PFO closurevsno-closure sample sets. Specificity for albumin-binding was assumed when binding to the negative control (anti-BL Ab) was less than binding to the anti-albumin Ab (ratio <0.5). Eight proteins were present in both sample sets and their abundance ratios and ROC AUC scores are given in Table 3. All 8 proteins present in both sample sets have been previously identified in HDL (26).
Mentions: Additional file 4 lists all the albumin-bound proteins and abundance ratios in PFO closure and no-closure samples. A total of 46 albumin-bound proteins were detected in PFO closure samples, 15 with an increased ratio (>1.2) and 13 with a decreased ratio (<0.8). Forty albumin-bound proteins were detected in the PFO no-closure samples, 9 with an increased ratio (>1.2) and 19 with a decreased ratio (<0.8). Eight proteins were present in both sample sets (Figure 2), and their abundance ratios and ROC AUC scores are given in Table 3. All 8 proteins present in both sample sets have been previously identified in HDL [26]. The ROC AUC scores and abundance ratios of the 8 proteins in common were very different between the PFO closure and no closure sample groups. ApoA-1 and ApoC-III had the highest ROC AUC scores in the closure group indicating good to excellent classification power between the baseline and 3–12 month follow up samples, indicating a significant difference. Abundance ratios (baseline/follow up) for these proteins were also higher in the PFO closure sample set than in the no closure sample set, with the ApoC-III B/FU abundance ratio almost 2× higher in the closure sample group. In the no closure group, kininogen had the most significant ROC AUC score and its abundance ratio was ca 1.6× higher than in the closure group.Figure 2

Bottom Line: 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.Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant.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.

View Article: PubMed Central - PubMed

Affiliation: Thermo Scientific BRIMS, 790 Memorial Dr, Cambridge, MA 02139 UK.

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.

No MeSH data available.


Related in: MedlinePlus