CoChat
Sign Up
Cited by 350

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Prelamin A Acts to Accelerate Smooth Muscle Cell Senescence and Is a Novel Biomarker of Human Vascular Aging

Ragnauth, Cassandra D., Warren, Derek T., Liu, Yiwen, McNair, Rosamund, Tajsic, Tamara, Figg, Nichola, Shroff, Rukshana, Skepper, Jeremy, Shanahan, Catherine M.·2010·Circulation
DOI 10.1161/circulationaha.109.902056
Open this paper in CoChat — free account

Abstract

Background— Hutchinson-Gilford progeria syndrome is a rare inherited disorder of premature aging caused by mutations in LMNA or Zmpste24 that disrupt nuclear lamin A processing, leading to the accumulation of prelamin A. Patients develop severe premature arteriosclerosis characterized by vascular smooth muscle cell (VSMC) calcification and attrition. Methods and Results— To determine whether defective lamin A processing is associated with vascular aging in the normal population, we examined the profile of lamin A expression in normal and aged VSMCs. In vitro, aged VSMCs rapidly accumulated prelamin A coincidently with nuclear morphology defects, and these defects were reversible by treatment with farnesylation inhibitors and statins. In human arteries, prelamin A accumulation was not observed in young healthy vessels but was prevalent in medial VSMCs from aged individuals and in atherosclerotic lesions, where it often colocalized with senescent and degenerate VSMCs. Prelamin A accumulation correlated with downregulation of the lamin A processing enzyme Zmpste24/FACE1, and FACE1 mRNA and protein levels were reduced in response to oxidative stress. Small interfering RNA knockdown of FACE1 reiterated the prelamin A–induced nuclear morphology defects characteristic of aged VSMCs, and overexpression of prelamin A accelerated VSMC senescence. We show that prelamin A acts to disrupt mitosis and induce DNA damage in VSMCs, leading to mitotic failure, genomic instability, and premature senescence. Conclusions— This study shows that prelamin A is a novel biomarker of VSMC aging and disease that acts to accelerate senescence. It therefore represents a novel target to ameliorate the effects of age-induced vascular dysfunction.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/circulationaha.109.902056

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Alterations of the nuclear lamina and production of an aberrant prelamin A isoform called progerin have been detected during normal human aging.

    “Alterations of the nuclear lamina and production of an aberrant prelamin A isoform called progerin have also been detected during normal human aging (Ragnauth et al., 2010; Scaffidi and Misteli, 2006).”

    From The Hallmarks of Aging (2013) · cites this paper as Ragnauth et al., 2010

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 40

  1. 10.1038/nrm1550 · DOI
  2. 10.1242/jcs.107.1.61 · DOI
  3. 10.1126/science.1084125 · DOI · Paper page
  4. 10.1101/gad.1652708 · DOI · Paper page
  5. 10.1002/humu.20315 · DOI
  6. 10.1136/jmg.2004.029751 · DOI
  7. 10.1073/pnas.0402943101 · DOI · Paper page
  8. 10.1016/j.exger.2004.02.002 · DOI
  9. 10.1126/science.1127168 · DOI · Paper page
  10. 10.1056/NEJMoa0706898 · DOI
  11. 10.1038/ncb1708 · DOI
  12. 10.1073/pnas.0511133103 · DOI
  13. 10.1073/pnas.0600012103 · DOI
  14. 10.1016/S1054-8807(01)00069-2 · DOI
  15. 10.1016/S1054-8807(98)00023-4 · DOI · Paper page
  16. 10.1074/jbc.M410075200 · DOI
  17. 10.1161/circ.100.21.2168 · DOI
  18. 10.1371/journal.pone.0001269 · DOI
  19. 10.1016/0921-8777(93)90010-E · DOI
  20. 10.1073/pnas.0505767102 · DOI
  21. 10.1073/pnas.0506001102 · DOI
  22. 10.1161/01.cir.0000096485.64373.c5 · DOI
  23. 10.1038/nature01631 · DOI
  24. 10.1161/01.atv.0000059406.92165.31 · DOI
  25. 10.1002/jcp.20791 · DOI
  26. 10.1093/hmg/11.7.769 · DOI
  27. 10.1073/pnas.0700854104 · DOI
  28. 10.1073/pnas.0611640104 · DOI
  29. 10.1073/pnas.0408558102 · DOI
  30. 10.1161/01.atv.0000146266.65820.a1 · DOI
  31. 10.1038/cdd.2008.47 · DOI · Paper page
  32. 10.1161/01.res.0000256837.40544.4a · DOI · Paper page
  33. Matturri L, Cazzullo A, Turconi P, Lavezzi AM. Cytogenetic aspects of cell proliferation in atherosclerotic plaques. Cardiologia. 1997; 42: 833–836.
  34. 10.1074/jbc.M308406200 · DOI
  35. 10.1161/01.cir.0000026393.47805.21 · DOI
  36. 10.1016/j.bbalip.2007.11.003 · DOI
  37. 10.1172/JCI28968 · DOI · Paper page
  38. 10.1126/science.1124875 · DOI
  39. 10.1073/pnas.0807840105 · DOI
  40. 10.1038/nm1786 · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Ragnauth, C. D., Warren, D. T., Liu, Y., McNair, R., Tajsic, T., Figg, N., Shroff, R., Skepper, J., & Shanahan, C. M.
Affiliations
From the British Heart Foundation Centre, Division of Cardiovascular Medicine, Kings College London (C.D.R., D.T.W., Y.L., T.T., C.M.S.), and Nephrology Unit (R.S.), Great Ormond Street Hospital, London, UK; Department of Medicine, Addenbrooke’s Hospital, Cambridge, UK (R.M., N.F.); and Imaging Centre, Department of Anatomy, University of Cambridge, Cambridge, UK (J.S.). Dr Ragnauth is currently affiliated with the Genomics CoreLab, University of Cambridge Metabolic Research Laboratories,...
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-05-25
Volume
121
Issue
20
Pages
2200-2210
ISSN
  • 0009-7322
  • 1524-4539
DOI
10.1161/circulationaha.109.902056
Cited by
350
References
3
Language
en

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