Evidence map›Paper›PMID 25060796›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Osteopontin-CD44v6 interaction mediates calcium deposition via phospho-Akt in valve interstitial cells from patients with noncalcified aortic valve sclerosis.

Paolo Poggio, Emanuela Branchetti, Juan B Grau, Eric K Lai, Robert C Gorman, Joseph H Gorman, Michael S Sacks, Joseph E Bavaria, Giovanni Ferrari

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

34 citing papers in PubMed, 60 citations in OpenAlex.

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  7. Atheroprotective Aspects of Heat Shock Proteins.International journal of molecular sciences · 2023
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  11. Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023
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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

9 authors at 1 institution in 1 country.

Paolo PoggioFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Emanuela BranchettiFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Juan B GrauFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Eric K LaiFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Robert C GormanFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Joseph H GormanFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Michael S SacksFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Joseph E BavariaFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.).
Giovanni FerrariFrom the Department of Surgery, Perelman School of Medicine at University of Pennsylvania, Philadelphia (P.P., E.B., J.B.G., E.K.L., R.C.G., J.H.G., J.E.B., G.F.); Centro Cardiologico Monzino IRCCS, Milan, Italy (P.P.); Columbia University-Valley Heart Center, Ridgewood, NJ (J.B.G.); and Department of Biomedical Engineering, University of Texas at Austin (M.S.S.). giovanni.ferrari@uphs.upenn.edu.
Centro Cardiologico Monzino · IT

Funding

Surgery to Prevent Post Infarction Ventricular RemodelingR01HL063954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GORMAN, ROBERT C · 2001 to 2018
$9.8M
Echocardiography to Predict Recurrent IMR After Surgical Mitral Valve ReplacementR01HL103723 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GORMAN, ROBERT C, HUNG, JUDY W · 2011 to 2020
$5.3M
NHLBI NIH HHS R01 HL063954NHLBI NIH HHS R01 HL103723
6 · The paper itself

Abstract

objectiveThe activation of valve interstitial cells (VICs) toward an osteogenic phenotype characterizes aortic valve sclerosis, the early asymptomatic phase of calcific aortic valve disease. Osteopontin is a phosphorylated acidic glycoprotein that accumulates within the aortic leaflets and labels VIC activation even in noncalcified asymptomatic patients. Despite this, osteopontin protects VICs against in vitro calcification. Here, we hypothesize that the specific interaction of osteopontin with CD44v6, and the related intracellular pathway, prevents calcium deposition in human-derived VICs from patients with aortic valve sclerosis. APPROACH AND

resultsOn informed consent, 23 patients and 4 controls were enrolled through the cardiac surgery and heart transplant programs. Human aortic valves and VICs were tested for osteogenic transdifferentiation, ex vivo and in vitro. Osteopontin-CD44 interaction was analyzed using proximity ligation assay and the signaling pathways investigated. A murine model based on angiotensin II infusion was used to mimic early pathological remodeling of the aortic valves. We report osteopontin-CD44 functional interaction as a hallmark of early stages of calcific aortic valve disease. We demonstrated that osteopontin-CD44 interaction mediates calcium deposition via phospho-Akt in VICs from patients with noncalcified aortic valve sclerosis. Finally, microdissection analysis of murine valves shows increased cusp thickness in angiotensin II-treated mice versus saline infused along with colocalization of osteopontin and CD44 as seen in human lesions.

conclusionsHere, we unveil a specific protein-protein association and intracellular signaling mechanisms of osteopontin. Understanding the molecular mechanisms of early VIC activation and calcium deposition in asymptomatic stage of calcific aortic valve disease could open new prospective for diagnosis and therapeutic intervention.

Indexed as

Angiotensin IIAnimalsAortic ValveAortic Valve StenosisBioreactorsBone Morphogenetic Protein 4CalcinosisCalciumCell TransdifferentiationDisease Models, AnimalDisease ProgressionHumansHyaluronan ReceptorsMaleMiceMice, Inbred C57BLAngiotensin IIBone Morphogenetic Protein 4CalciumCD44v6 antigenHyaluronan ReceptorsOsteopontinProto-Oncogene Proteins c-aktSpp1 protein, mouseaortic valveosteopontin

Identifiers

PMID25060796
PMCPMC6580848
OpenAlexW2085572466

What OpenQuestion holds

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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.