CoChat
Sign Up
Cited by 97Autophagy in Disease and TherapyMitochondrial Function and PathologyTelomeres, Telomerase, and Senescence

Downregulation of dynamin-related protein 1 contributes to impaired autophagic flux and angiogenic function in senescent endothelial cells

Lin, Jing-Rong, Shen, Wei-Li, Yan, Chen, Gao, Ping-Jin·2015·Arteriosclerosis Thrombosis and Vascular Biology
DOI 10.1161/atvbaha.115.305706
Open this paper in CoChat — free account

Abstract

OBJECTIVE: Recent studies have shown that altered mitochondrial dynamics impairs the function in senescent endothelial cells (ECs). However, the underlying molecular mechanism remains to be elucidated. Herein, we investigated the role and underlying mechanism of mitochondrial fission protein dynamin-related protein 1 (DRP1) in vascular aging. APPROACH AND RESULTS: We found that DRP1 expression is decreased in senescent ECs, accompanied with long interconnected mitochondria and impaired angiogenic function. In addition, there was marked increase of autophagosomes but not of autolysosomes (assessed as punctate dual fluorescent mCherry-GFP (green fluorescent protein) tandem-tagged light chain 3 expression) in senescent ECs, indicating impaired autophagic flux. DRP1 knockdown or pharmacological inhibition in young ECs resulted in elongated mitochondria, suppressed autophagic flux, premature senescence, and impaired angiogenic function. In contrast, adenoviral-mediated overexpression of DRP1 in senescent ECs restored autophagic flux and improved angiogenic function. EC senescence was associated with the increase of mitochondrial reactive oxygen species and antioxidant N-acetyl-cysteine restored autophagosome clearance and improved angiogenic function. Consistently, en face staining of old rat thoracic aorta revealed a decrease of DRP1 expression and increase of autophagosomes accumulation. Furthermore, in vivo knockdown of Drp1 in common carotid arteries significantly impaired the autophagosome clearance. Importantly, downregulation of Drp1 directly abrogated microvessels outgrowth from ex vivo aortic rings. CONCLUSIONS: These results suggest that loss of DRP1 during senescence exacerbates ECs dysfunction by increasing mitochondrial reactive oxygen species and subsequently inhibiting autophagic flux.

Integrity signals

Registry

Crossref · 10.1161/atvbaha.115.305706

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Lysosomal dysfunction has been documented in replicative and oxidative stress-induced senescence and in both cases was associated with buildup of autophagosomes and related markers (e.g., LC3-II, p62).

    “Consistent with our findings (Fig. 5,Fig. S3), lysosomal dysfunction has been documented in replicative [74] and oxidative stress-induced senescence [57] and in both cases was associated with the buildup of autophagosomes and related markers (e.g. LC3-II, p62).”

    From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [74]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Lin, J.-R., Shen, W.-L., Yan, C., & Gao, P.-J.
Affiliations
From the Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China (J.-R.L., P.-J.G.); Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, China (W.-L.S., C.Y., P.-J.G.).
Venue
Arteriosclerosis Thrombosis and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-06
Volume
35
Issue
6
Pages
1413-1422
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.115.305706
OpenAlex
W2099361886
Cited by
97
References
45
Citations by year
2026: 4 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 10 · 2017: 10 · 2016: 8 · 2015: 1
FWCI
7.58
Type
journal article
Language
en
Open access
closed
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
Drp1, endothelial cell senescence, autophagic flux, angiogenesis, mitochondrial fission, mitochondrial dynamics, vascular aging, autophagosome clearance, reactive oxygen species, N-acetylcysteine, premature senescence
MeSH terms
Animals, Autophagy, Humans, Microtubule-Associated Proteins, Mitochondria, Muscle, Muscle, Smooth, Vascular, Rats, Inbred WKY, Umbilicus, Veins, Down-Regulation, Cellular Senescence, Reactive Oxygen Species, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review