Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure.
Aged
Apolipoproteins M
/ blood
Biomarkers
/ blood
Down-Regulation
Female
Heart Failure
/ blood
Humans
Lipoproteins, HDL
/ blood
Lysophospholipids
/ blood
Male
Middle Aged
Prognosis
Proteome
Proteomics
Randomized Controlled Trials as Topic
Registries
Risk Assessment
Risk Factors
Sphingosine
/ analogs & derivatives
Time Factors
United States
apolipoproteins M
heart failure
lipoproteins, HDL
sphingosine-1-phosphate
survival
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
05 05 2020
05 05 2020
Historique:
pubmed:
3
4
2020
medline:
8
6
2021
entrez:
3
4
2020
Statut:
ppublish
Résumé
Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61]; Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
Sections du résumé
BACKGROUND
Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models.
METHODS
In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure.
RESULTS
In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61];
CONCLUSIONS
Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
Identifiants
pubmed: 32237898
doi: 10.1161/CIRCULATIONAHA.119.045323
pmc: PMC7200273
mid: NIHMS1581038
doi:
Substances chimiques
APOM protein, human
0
Apolipoproteins M
0
Biomarkers
0
Lipoproteins, HDL
0
Lysophospholipids
0
Proteome
0
sphingosine 1-phosphate
26993-30-6
Sphingosine
NGZ37HRE42
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1463-1476Subventions
Organisme : NHLBI NIH HHS
ID : U10 HL110338
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL107594
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL094307
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL102222
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007081
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL104106
Pays : United States
Organisme : NHLBI NIH HHS
ID : R61 HL146390
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL136730
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058969
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119962
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL138262
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100026C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL121510
Pays : United States
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