Evidence map›Paper›PMID 25009290›Full record

ArticleCirculation research2014

PGC-1α induces SPP1 to activate macrophages and orchestrate functional angiogenesis in skeletal muscle.

Glenn C Rowe, Srilatha Raghuram, Cholsoon Jang, Janice A Nagy, Ian S Patten, Amrita Goyal, Mun Chun Chan, Laura X Liu, Aihua Jiang, Katherine C Spokes and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Pooled it
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  10. Monocyte-derived macrophages and their roles in ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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5 more citing papers are in PubMed but not listed here.

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

14 authors at 1 institution in 1 country.

Glenn C RoweFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Srilatha RaghuramFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Cholsoon JangFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Janice A NagyFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Ian S PattenFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Amrita GoyalFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Mun Chun ChanFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Laura X LiuFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Aihua JiangFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Katherine C SpokesFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
David BeelerFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Harold DvorakFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
William C AirdFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Zolt AranyFrom the Department of Medicine, Cardiovascular Institute (G.C.R., S.R., C.J., I.S.P., A.G., M.C.C., L.X.L., A.J., Z.A.), Center for Vascular Biology Research (J.A.N., K.C.S., D.B., H.D., W.C.A., Z.A.), and Department of Pathology (J.A.N., H.D.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. zarany@bidmc.harvard.edu.
Anna Needs Neuroblastoma Answers · US

Funding

VASCULAR TOPOGRAPHY OF CD39/NTPDASESP01HL076540 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI AIRD, WILLIAM C · 2004 to 2014
$20.3M
The Role of PlGF in Normal and Neoplastic AngiogenesisP01CA092644 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI DVORAK, HAROLD FISHER · 2002 to 2013
$17.2M
Training Program in Cardiovascular ResearchT32HL007374 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MITTLEMAN, MURRAY A · 1985 to 2019
$7.9M
PGC-1 Coactivators in Muscle Angiogenesis IschemiaR01HL094499 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ARANY, ZOLTAN P · 2010 to 2018
$3.7M
Regulation of Mitochondria by Exercise and PGC-1 Coactivators in Skeletal MuscleK01AR062128 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, GLENN CAMERON · 2012 to 2016
$621k
Building Vascularized Skeletal Muscle for Tissue Engineering/RegenerationR21AR063347 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI ARANY, ZOLTAN P, BISCHOFF, JOYCE E. · 2013 to 2014
$427k
NCI NIH HHS P01 CA092644NCI NIH HHS P01 CA92644NHLBI NIH HHS HL076540NHLBI NIH HHS P01 HL076540NHLBI NIH HHS R01 HL094499NHLBI NIH HHS T32 HL007374NIAMS NIH HHS K01 AR062128NIAMS NIH HHS KO1 AR062128
6 · The paper itself

Abstract

rationaleMechanisms of angiogenesis in skeletal muscle remain poorly understood. Efforts to induce physiological angiogenesis hold promise for the treatment of diabetic microvascular disease and peripheral artery disease but are hindered by the complexity of physiological angiogenesis and by the poor angiogenic response of aged and patients with diabetes mellitus. To date, the best therapy for diabetic vascular disease remains exercise, often a challenging option for patients with leg pain. Peroxisome proliferation activator receptor-γ coactivator-1α (PGC-1α), a powerful regulator of metabolism, mediates exercise-induced angiogenesis in skeletal muscle.

objectiveTo test whether, and how, PGC-1α can induce functional angiogenesis in adult skeletal muscle. METHODS AND

resultsHere, we show that muscle PGC-1α robustly induces functional angiogenesis in adult, aged, and diabetic mice. The process involves the orchestration of numerous cell types and leads to patent, nonleaky, properly organized, and functional nascent vessels. These findings contrast sharply with the disorganized vasculature elicited by induction of vascular endothelial growth factor alone. Bioinformatic analyses revealed that PGC-1α induces the secretion of secreted phosphoprotein 1 and the recruitment of macrophages. Secreted phosphoprotein 1 stimulates macrophages to secrete monocyte chemoattractant protein-1, which then activates adjacent endothelial cells, pericytes, and smooth muscle cells. In contrast, induction of PGC-1α in secreted phosphoprotein 1(-/-) mice leads to immature capillarization and blunted arteriolarization. Finally, adenoviral delivery of PGC-1α into skeletal muscle of either young or old and diabetic mice improved the recovery of blood flow in the murine hindlimb ischemia model of peripheral artery disease.

conclusionsPGC-1α drives functional angiogenesis in skeletal muscle and likely recapitulates the complex physiological angiogenesis elicited by exercise.

Indexed as

Macrophage ActivationNeovascularization, PhysiologicAdenoviridaeAnimalsCell CommunicationCell LineCell MovementChemokine CCL2Diabetes MellitusDisease Models, AnimalGenetic TherapyGenetic VectorsHumansHuman Umbilical Vein Endothelial CellsIschemiaMacrophagesCCL2 protein, humanChemokine CCL2FLT1 protein, humanOsteopontinPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseSpp1 protein, mouseTranscription FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1VEGFA protein, humanangiogenesis effectcytokinesgene action regulationgenetic therapyintercellular signaling peptides and proteinsmacrophagesmuscleosteopontinperipheral arterial diseasePGC-1alpha protein, mouseskeletal

Identifiers

PMID25009290
PMCPMC4524357
OpenAlexW2076724486

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Registered trials

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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.