Evidence map›Paper›PMID 36073351›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2022

The Nonproteolytic Intracellular Domain of Membrane-Type 1 Matrix Metalloproteinase Coordinately Modulates Abdominal Aortic Aneurysm and Atherosclerosis in Mice-Brief Report.

Michele Silvestro, Cristobal F Rivera, Dornazsadat Alebrahim, John Vlahos, Muhammad Yogi Pratama, Cuijie Lu, Claudia Tang, Zander Harpel, Rayan Sleiman Tellaoui, Ariadne L Zias and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2022. 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
1.4field-weighted citation impact, top 18% 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, 9 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

15 authors at 2 institutions in 1 country.

Michele SilvestroDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).ORCID 0000-0003-1151-2215
Cristobal F RiveraDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).ORCID 0000-0001-9648-9880
Dornazsadat AlebrahimDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
John VlahosDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Muhammad Yogi PratamaDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Cuijie LuDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Claudia TangDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Zander HarpelDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Rayan Sleiman TellaouiDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Ariadne L ZiasDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Delphina J MaldonadoDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Devon ByrdDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).
Mukundan AtturDivision of Rheumatology, Department of Medicine (C.L., M.A., P.M.), New York University Langone Medical Center, New York.ORCID 0000-0001-7080-8118
Paolo MignattiDivision of Rheumatology, Department of Medicine (C.L., M.A., P.M.), New York University Langone Medical Center, New York.
Bhama RamkhelawonDivision of Vascular and Endovascular Surgery, Department of Surgery (M.S., C.F.R., D.A., J.V., M.Y.P., C.T., Z.H., R.S.T., A.L.Z., D.J.M., D.B., B.R.).ORCID 0000-0002-9087-0995
United States Nuclear Regulatory Commission · USNYU Langone Health · US

Funding

Spatiotemporal checkpoints of macrophages in aortic aneurysms- RenewalR01HL146627 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Bhama Ramkhelawon · 2019 to 2026
$6.1M
NON-PROTEOLYTIC INTERACTIONS OF TIMP-2 AND MT1-MMPR01CA136715 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MIGNATTI, PAOLO · 2009 to 2014
$2.3M
Physiological role of MT1-MMP-mediated, proteolysis-independent signaling in vivoR21AG033735 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MIGNATTI, PAOLO · 2009 to 2011
$414k
Control of bone homeostasis by MT1-MMP signalingR21AR069240 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ABRAMSON, STEVEN B · 2016 to 2017
$408k
NCI NIH HHS R01 CA136715NHLBI NIH HHS R01 HL146627NIAMS NIH HHS R21 AR069240NIA NIH HHS R21 AG033735
6 · The paper itself

Abstract

backgroundMT1-MMP (membrane-type 1 matrix metalloproteinase, MMP-14) is a transmembrane-anchored protein with an extracellular proteinase domain and a cytoplasmic tail devoid of proteolytic functions but capable of mediating intracellular signaling that regulates tissue homeostasis. MT1-MMP extracellular proteolytic activity has been shown to regulate pathological remodeling in aortic aneurysm and atherosclerosis. However, the role of the nonproteolytic intracellular domain of MT1-MMP in vascular remodeling in abdominal aortic aneurysms (AAA) is unknown.

methodsWe generated a mutant mouse that harbors a point mutation (Y573D) in the MT1-MMP cytoplasmic domain that abrogates the MT1-MMP signaling function without affecting its proteolytic activity. These mice and their control wild-type littermates were subjected to experimental AAA modeled by angiotensin II infusion combined with PCSK9 (proprotein convertase subtilisin/kexin type 9) overexpression and high-cholesterol feeding.

resultsThe mutant mice developed more severe AAA than the control mice, with concomitant generation of intraaneurysmal atherosclerotic lesions and dramatically increased macrophage infiltration and elastin degradation. Aortic lesion-associated and bone marrow-derived macrophages from the mutant mice exhibited an enhanced inflammatory state and expressed elevated levels of proinflammatory Netrin-1, a protein previously demonstrated to promote both atherosclerosis and AAA.

conclusionsOur findings show that the cytoplasmic domain of MT1-MMP safeguards from AAA and atherosclerotic plaque development through a proteolysis-independent signaling mechanism associated with Netrin-1 expression. This unexpected function of MT1-MMP unveils a novel mechanism of synchronous onset of AAA and atherogenesis and highlights its importance in the control of vascular wall homeostasis.

Indexed as

Aortic Aneurysm, AbdominalAtherosclerosisAngiotensin IIAnimalsCholesterolElastinMatrix Metalloproteinase 14MiceNetrin-1Proprotein Convertase 9SubtilisinsAngiotensin IICholesterolElastinMatrix Metalloproteinase 14Netrin-1PCSK9 protein, humanProprotein Convertase 9Subtilisinsangiotensinaortic aneurysm, abdominalatherosclerosismacrophagesmatrix metalloproteinase 14matrix metalloproteinasesNetrin-1

Identifiers

PMID36073351
PMCPMC9993845
OpenAlexW4294992145

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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.