Evidence map›Paper›PMID 26926601›Full record

ArticleAtherosclerosis2016

Restoration of autophagy in endothelial cells from patients with diabetes mellitus improves nitric oxide signaling.

Jessica L Fetterman, Monica Holbrook, Nir Flint, Bihua Feng, Rosa Bretón-Romero, Erika A Linder, Brittany D Berk, Mai-Ann Duess, Melissa G Farb, Noyan Gokce and 3 more

Open access · greenAbstract read
In one paragraph

Article in Atherosclerosis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
8.8field-weighted citation impact, top 2% 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

59 citing papers in PubMed, 107 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  5. Autophagy as a Guardian of Vascular Niche Homeostasis.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
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

13 authors at 1 institution in 1 country.

Jessica L FettermanEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Monica HolbrookEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Nir FlintEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Bihua FengEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Rosa Bretón-RomeroEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Erika A LinderEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Brittany D BerkEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Mai-Ann DuessEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Melissa G FarbEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Noyan GokceEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Orian S ShirihaiEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Naomi M HamburgEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA. Electronic address: nhamburg@bu.edu.
Joseph A VitaEvans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Boston University · US

Funding

Redox regulation in Endothelial Progenitor CellsP01HL081587 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALSH, KENNETH · 2005 to 2015
$21.5M
Multidisciplinary Training in Cardiovascular ResearchT32HL007224 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HAMBURG, NAOMI MIRIAM, WAINFORD, RICHARD DAVID · 1985 to 2020
$12.3M
Boston University Medical Center Leadership Program in Vascular MedicineK12HL083781 · NHLBI · BOSTON MEDICAL CENTER · PI EBERHARDT, ROBERT THOMAS · 2007 to 2013
$3.4M
Mitochondrial Dynamics and UCP2 - Endothelial Dysfunction in Human ObesityR01HL115391 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HAMBURG, NAOMI MIRIAM · 2013 to 2017
$2.8M
Adipose inflammation, mitochondrial function & endothelial phenotypes in obesityR01HL114675 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GOKCE, NOYAN · 2012 to 2016
$2.3M
Endothelial Insulin Resistance, Inflammation and Vascular Function in DiabetesR01HL102299 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HAMBURG, NAOMI MIRIAM · 2010 to 2014
$2.0M
MicroRNA Profile in Peripheral Artery DiseaseR21HL109790 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HAMBURG, NAOMI MIRIAM · 2012 to 2013
$455k
NHLBI NIH HHS HL081587NHLBI NIH HHS HL102299NHLBI NIH HHS HL109790NHLBI NIH HHS HL11539NHLBI NIH HHS HL115775NHLBI NIH HHS HL81587NHLBI NIH HHS K12 HL083781NHLBI NIH HHS P01 HL081587NHLBI NIH HHS R01 HL102299NHLBI NIH HHS R01 HL114675NHLBI NIH HHS R01 HL115391NHLBI NIH HHS R21 HL109790NHLBI NIH HHS T32 HL007224
6 · The paper itself

Abstract

backgroundEndothelial dysfunction contributes to cardiovascular disease in diabetes mellitus. Autophagy is a multistep mechanism for the removal of damaged proteins and organelles from the cell. Under diabetic conditions, inadequate autophagy promotes cellular dysfunction and insulin resistance in non-vascular tissue. We hypothesized that impaired autophagy contributes to endothelial dysfunction in diabetes mellitus. METHODS AND

resultsWe measured autophagy markers and endothelial nitric oxide synthase (eNOS) activation in freshly isolated endothelial cells from diabetic subjects (n = 45) and non-diabetic controls (n = 41). p62 levels were higher in cells from diabetics (34.2 ± 3.6 vs. 20.0 ± 1.6, P = 0.001), indicating reduced autophagic flux. Bafilomycin inhibited insulin-induced activation of eNOS (64.7 ± 22% to -47.8 ± 8%, P = 0.04) in cells from controls, confirming that intact autophagy is necessary for eNOS signaling. In endothelial cells from diabetics, activation of autophagy with spermidine restored eNOS activation, suggesting that impaired autophagy contributes to endothelial dysfunction (P = 0.01). Indicators of autophagy initiation including the number of LC3-bound puncta and beclin 1 expression were similar in diabetics and controls, whereas an autophagy terminal phase indicator, the lysosomal protein Lamp2a, was higher in diabetics. In endothelial cells under diabetic conditions, the beneficial effect of spermidine on eNOS activation was blocked by autophagy inhibitors bafilomycin or 3-methyladenine. Blocking the terminal stage of autophagy with bafilomycin increased p62 (P = 0.01) in cells from diabetics to a lesser extent than in cells from controls (P = 0.04), suggesting ongoing, but inadequate autophagic clearance.

conclusionInadequate autophagy contributes to endothelial dysfunction in patients with diabetes and may be a target for therapy of diabetic vascular disease.

Indexed as

AdenosineAdultAgedAutophagyBiomarkersCase-Control StudiesCells, CulturedCell SeparationDiabetes Mellitus, Type 2Diabetic AngiopathiesEndothelial CellsFemaleHumansMacrolidesMaleMiddle Aged3-methyladenosineAdenosinebafilomycin A1BiomarkersMacrolidesNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanSpermidineAutophagyDiabetes mellitusEndothelial cells

Identifiers

PMID26926601
PMCPMC4913892
OpenAlexW2261470140

What OpenQuestion holds

Textmetadata
LicenceTDM
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.