Evidence map›Paper›PMID 39197028›Full record

ArticleCardiovascular research2024

Insulin receptors in vascular smooth muscle cells regulate plaque stability of atherosclerosis.

Qian Li, Jialin Fu, Kyoungmin Park, Hetal Shah, Qin Li, I Hsien Wu, George L King

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

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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

7 authors.

Qian LiDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.ORCID 0000-0003-1358-5469
Jialin FuDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Kyoungmin ParkDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Hetal ShahDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Qin LiDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
I Hsien WuDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.ORCID 0000-0002-2563-7505
George L KingDianne Nunnally Hoppes Laboratory for Diabetes Complications, Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
SELECTIVE INSULIN RESISTANCE--DIABETIC VASCULAR DISEASER01DK053105 · NIDDK · JOSLIN DIABETES CENTER · PI KING, GEORGE L · 1997 to 2017
$5.0M
Special BD LSRFortessaS10OD021740 · OD · JOSLIN DIABETES CENTER · PI SERWOLD, THOMAS F · 2016 to 2016
$363k
Beatson Foundation GiftDianne Nunnally Hoppes Fund 5P30DK036836NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK053105NIH HHS R01-DK-053105NIH HHS S10 OD021740
6 · The paper itself

Abstract

aimsIncreased prevalence of acute myocardial infarction related to diabetes and insulin resistance is associated with an elevated risk of unstable atherosclerotic plaques, which are characterized by reduced vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM) and increased inflammation. Thus, insulin resistance may reduce plaque stability, as deleting insulin receptors (IRs) in VSMCs decreases their proliferation and enhances apoptosis. METHODS AND

resultsDirect effects of insulin on VSMCs to alter plaque composition were studied using mice with double knockout of ApoE and IR genes in VSMCs with SMIRKO/ApoE-/-, Myh11-CreERT2EYFP+/ApoE-/-, and Myh11-CreERT2EYFP+IRKO/ApoE-/- mice, which were also used for lineage tracing studies. Compared with ApoE-/- mice, SMIRKO/ApoE-/- mice exhibited more atherosclerotic plaques, which contained less VSMCs and collagen but increased levels of VSMC apoptosis and necrotic areas. Lineage tracing studies showed that Icam1+ Vcam1+ VSMC was inflammatory, which increased in the aortas of Myh11-CreERT2EYFP+IRKO/ApoE-/- mice compared with control mice. Isolated VSMCs lacking IRs expressed higher inflammatory cytokines than cells with IRs. Cell-based studies indicated that insulin's anti-apoptotic and pro-proliferative effects in VSMCs were mediated via activation of the IR/Akt pathway, which were decreased in VSMCs from SMIRKO or high-fat diet mice. An analysis of the IR targets that regulated inflammatory cytokines in VSMCs showed that thrombospondin 1 (Thbs1) and Mmp2 were consistently increased with a loss of IRs. Insulin inhibited Thbs1 expression, but not Mmp2 expression, through p-Akt/p-FoxO1 pathways in VSMCs from ApoE-/- mice, and was impaired in cells from SMIRKO/ApoE-/- mice. Thbs1 further induced Icam1 and Mmp2 expressions in VSMCs.

conclusionInsulin via IRs has significant actions in VSMCs to decrease inflammation, apoptosis, and ECM turnover via the activation of Akt and FoxO1 pathways. The inhibition of insulin actions and related pathways related to insulin resistance and diabetes may contribute to the formation of unstable atherosclerotic plaques.

Indexed as

Aortic DiseasesApoptosisAtherosclerosisCell ProliferationDisease Models, AnimalMice, Inbred C57BLMice, Knockout, ApoEMuscle, Smooth, VascularMyocytes, Smooth MusclePlaque, AtheroscleroticReceptor, InsulinSignal TransductionAnimalsAortaApolipoproteins ECells, CulturedApoe protein, mouseApolipoproteins EIgf1r protein, mouseInflammation MediatorsInsulinMatrix Metalloproteinase 2Proto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptor, InsulinThbs1 protein, mouseThrombospondin 1AtherosclerosisInsulin receptorSmooth muscle cellsThrombospondin 1

Identifiers

PMID39197028
PMCPMC11646105

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.