Evidence map›Paper›PMID 26232205›Full record

ArticleCirculation. Heart failure2015

Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages.

Shun He, Benjamin G Chousterman, Ashley Fenn, Atsushi Anzai, Manfred Nairz, Martin Brandt, Ingo Hilgendorf, Yuan Sun, Yu-Xiang Ye, Yoshiko Iwamoto and 6 more

Open access · hybridAbstract read
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In one paragraph

Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.4field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Shun HeFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Benjamin G ChoustermanFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Ashley FennFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Atsushi AnzaiFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Manfred NairzFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Martin BrandtFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Ingo HilgendorfFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Yuan SunFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Yu-Xiang YeFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Yoshiko IwamotoFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Benoit TricotFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Ralph WeisslederFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Colin MacpheeFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Peter LibbyFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Matthias NahrendorfFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
Filip K SwirskiFrom the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.). fswirski@mgh.harvard.edu.
GlaxoSmithKline (United States) · USCenter for Systems Biology · USHarvard University · US

Funding

Monocyte Heterogeneity in Experimental and Human AtherosclerosisR01HL095612 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SWIRSKI, FILIP K · 2009 to 2016
$3.4M
Innate Response Activator B cells in Bacterial Lung InfectionR56AI104695 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SWIRSKI, FILIP K · 2013 to 2013
$403k
NHLBI NIH HHS 1R01HL095612NHLBI NIH HHS R01 HL095612NIAID NIH HHS R56 AI104695NIAID NIH HHS R56AI104695
6 · The paper itself

Abstract

backgroundHealing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease. Elevated Lp-PLA2 levels associate with increased risk of cardiovascular events across diverse patient populations, but the mechanisms by which the enzyme elicits its effects remain unclear. This study tested the role of Lp-PLA2 in healing after MI. METHODS AND

resultsIn response to MI, Lp-PLA2 levels markedly increased in the circulation. To test the functional importance of Lp-PLA2, we generated chimeric mice whose bone marrow-derived leukocytes were Lp-PLA2-deficient (bmLp-PLA2 (-/-)). Compared with wild-type controls, bmLp-PLA2 (-/-) mice subjected to MI had lower serum levels of inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and decreased number of circulating inflammatory myeloid cells. Accordingly, bmLp-PLA2 (-/-) mice developed smaller and less inflamed infarcts with reduced numbers of infiltrating neutrophils and inflammatory Ly-6C(high) monocytes. During the later, reparative phase, infarcts of bmLp-PLA2 (-/-) mice contained Ly-6C(low) macrophages with a skewed M2-prone gene expression signature, increased collagen deposition, fewer inflammatory cells, and improved indices of angiogenesis. Consequently, the hearts of bmLp-PLA2 (-/-) mice healed more efficiently, as determined by improved left ventricle remodeling and ejection fraction.

conclusionsLp-PLA2 augments the inflammatory response after MI and antagonizes healing by disrupting the balance between inflammation and repair, providing a rationale for focused study of ventricular function and heart failure after targeting this enzyme acutely in MI.

Indexed as

Gene Expression Regulation1-Alkyl-2-acetylglycerophosphocholine EsteraseAnimalsDisease Models, AnimalFemaleFlow CytometryHeart VentriclesMacrophagesMagnetic Resonance Imaging, CineMiceMice, Inbred C57BLMyocardial InfarctionReverse Transcriptase Polymerase Chain ReactionRNAVentricular RemodelingWound Healing1-Alkyl-2-acetylglycerophosphocholine EsteraseRNAheart failureinflammationmacrophagesmonocytesmyocardial infarction

Identifiers

PMID26232205
PMCPMC4568849
OpenAlexW2130327902

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.