High-density lipoprotein carries markers that track with recovery from stroke

Deanna L. Plubell, Alex M. Fenton, Sara Rosario, Paige Bergstrom, Phillip A. Wilmarth, Wayne M. Clark, Neil A. Zakai, Joseph F. Quinn, Jessica Minnier, Nabil J. Alkayed, Sergio Fazio, Nathalie Pamir

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: Prospective cohort studies question the value of HDL-C (high-density lipoprotein cholesterol) for stroke risk prediction. Objective: Investigate the relationship between long-term functional recovery and HDL proteome and function. Methods and Results: Changes in HDL protein composition and function (cholesterol efflux capacity) in patients after acute ischemic stroke at 2 time points (24 hours, 35 patients; 96 hours, 20 patients) and in 35 control subjects were measured. The recovery from stroke was assessed by 3 months, the National Institutes of Health Stroke Scale and modified Rankin scale scores. When compared with control subject after adjustments for sex and HDL-C levels, 12 proteins some of which participate in acute phase response and platelet activation (APMAP [adipocyte plasma membrane-associated protein], GPLD1 [phosphate inositol-glycan specific phospholipase D], APOE [apolipoprotein E], IHH [Indian hedgehog protein], ITIH4 [inter-alpha-trypsin inhibitor chain H4], SAA2 [serum amyloid A2], APOA4 [apolipoprotein A-IV], CLU [clusterin], ANTRX2 [anthrax toxin receptor 2], PON1 [serum paraoxonase/arylesterase], SERPINA1 [alpha-1-antitrypsin], and APOF [apolipoprotein F]) were significantly (adjusted P<0.05) altered in stroke HDL at 96 hours. The first 8 of these proteins were also significantly altered at 24 hours. Consistent with inflammatory remodeling, cholesterol efflux capacity was reduced by 32% (P<0.001) at both time points. Baseline stroke severity adjusted regression model showed that changes within 96-hour poststroke in APOF, APOL1, APMAP, APOC4 (apolipoprotein C4), APOM (apolipoprotein M), PCYOX1 (prenylcysteine oxidase 1), PON1, and APOE correlate with stroke recovery scores (R2=0.38-0.73, adjusted P<0.05). APOF (R2=0.73) and APOL1 (R2=0.60) continued to significantly correlate with recovery scores after accounting for tPA (tissue-type plasminogen activator) treatment. Conclusions: Changes in HDL proteins during early acute phase of stroke associate with recovery. Monitoring HDL proteins may provide clinical biomarkers that inform on stroke recuperation.

Original languageEnglish (US)
Pages (from-to)1274-1287
Number of pages14
JournalCirculation research
DOIs
StateAccepted/In press - 2020

Keywords

  • biomarkers
  • cholesterol
  • proteomics
  • stroke

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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