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Reduced Apolipoprot...
Reduced Apolipoprotein M and Adverse Outcomes across the Spectrum of Human Heart Failure
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- Chirinos, Julio A. (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Zhao, Lei (författare)
- Bristol-Myers Squibb
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- Jia, Yi (författare)
- SomaLogic
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- Frej, Cecilia (författare)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Adamo, Luigi (författare)
- Washington University in St. Louis
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- Mann, Douglas (författare)
- Washington University in St. Louis
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- Shewale, Swapnil V. (författare)
- Hospital of the University of Pennsylvania,University of Pennsylvania
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- Millar, John S. (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Rader, Daniel J. (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- French, Benjamin (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Brandimarto, Jeff (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Margulies, Kenneth B. (författare)
- Hospital of the University of Pennsylvania,University of Pennsylvania
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- Parks, John S. (författare)
- Wake Forest University
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- Wang, Zhaoqing (författare)
- Bristol-Myers Squibb
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- Seiffert, Dietmar A. (författare)
- Bristol-Myers Squibb
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- Fang, James (författare)
- University of Utah
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- Sweitzer, Nancy (författare)
- University of Arizona
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- Chistoffersen, Christina (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Dahlbäck, Björn (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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- Car, Bruce D. (författare)
- Bristol-Myers Squibb
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- Gordon, David A. (författare)
- Bristol-Myers Squibb
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- Cappola, Thomas P. (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Javaheri, Ali (författare)
- Washington University in St. Louis
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(creator_code:org_t)
- 2020
- 2020
- Engelska 14 s.
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Ingår i: Circulation. - 0009-7322. ; , s. 1463-1476
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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]; P<0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58-0.67]; P<0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69-0.88]; P<0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76-0.94]; P=0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated (R=0.81, P<0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- apolipoproteins M
- heart failure
- lipoproteins, HDL
- sphingosine-1-phosphate
- survival
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Chirinos, Julio ...
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Zhao, Lei
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Jia, Yi
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Frej, Cecilia
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Adamo, Luigi
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Mann, Douglas
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visa fler...
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Shewale, Swapnil ...
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Millar, John S.
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Rader, Daniel J.
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French, Benjamin
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Brandimarto, Jef ...
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Margulies, Kenne ...
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Parks, John S.
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Wang, Zhaoqing
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Seiffert, Dietma ...
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Fang, James
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Sweitzer, Nancy
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Chistoffersen, C ...
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Dahlbäck, Björn
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Car, Bruce D.
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Gordon, David A.
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Cappola, Thomas ...
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Javaheri, Ali
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Circulation
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