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ADAM12: a genetic modifier of preclinical peripheral arterial disease.

Publication ,  Journal Article
Dokun, AO; Chen, L; Okutsu, M; Farber, CR; Hazarika, S; Jones, WS; Craig, D; Marchuk, DA; Lye, RJ; Shah, SH; Annex, BH
Published in: Am J Physiol Heart Circ Physiol
September 2015

In prior studies from multiple groups, outcomes following experimental peripheral arterial disease (PAD) differed considerably across inbred mouse strains. Similarly, in humans with PAD, disease outcomes differ, even when there are similarities in risk factors, disease anatomy, arteriosclerotic burden, and hemodynamic measures. Previously, we identified a locus on mouse chromosome 7, limb salvage-associated quantitative trait locus 1 (LSq-1), which was sufficient to modify outcomes following experimental PAD. We compared expression of genes within LSq-1 in Balb/c mice, which normally show poor outcomes following experimental PAD, with that in C57Bl/6 mice, which normally show favorable outcomes, and found that a disintegrin and metalloproteinase gene 12 (ADAM12) had the most differential expression. Augmentation of ADAM12 expression in vivo improved outcomes following experimental PAD in Balb/c mice, whereas knockdown of ADAM12 made outcomes worse in C57Bl/6 mice. In vitro, ADAM12 expression modulates endothelial cell proliferation, survival, and angiogenesis in ischemia, and this appeared to be dependent on tyrosine kinase with Ig-like and EGF-like domain 2 (Tie2) activation. ADAM12 is sufficient to modify PAD severity in mice, and this likely occurs through regulation of Tie2.

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Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

September 2015

Volume

309

Issue

5

Start / End Page

H790 / H803

Location

United States

Related Subject Headings

  • Receptor, TIE-2
  • Peripheral Arterial Disease
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Endothelium, Vascular
  • Endothelial Cells
  • Cell Proliferation
  • Cardiovascular System & Hematology
 

Citation

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Dokun, A. O., Chen, L., Okutsu, M., Farber, C. R., Hazarika, S., Jones, W. S., … Annex, B. H. (2015). ADAM12: a genetic modifier of preclinical peripheral arterial disease. Am J Physiol Heart Circ Physiol, 309(5), H790–H803. https://doi.org/10.1152/ajpheart.00803.2014
Dokun, Ayotunde O., Lingdan Chen, Mitsuharu Okutsu, Charles R. Farber, Surovi Hazarika, W Schuyler Jones, Damian Craig, et al. “ADAM12: a genetic modifier of preclinical peripheral arterial disease.Am J Physiol Heart Circ Physiol 309, no. 5 (September 2015): H790–803. https://doi.org/10.1152/ajpheart.00803.2014.
Dokun AO, Chen L, Okutsu M, Farber CR, Hazarika S, Jones WS, et al. ADAM12: a genetic modifier of preclinical peripheral arterial disease. Am J Physiol Heart Circ Physiol. 2015 Sep;309(5):H790–803.
Dokun, Ayotunde O., et al. “ADAM12: a genetic modifier of preclinical peripheral arterial disease.Am J Physiol Heart Circ Physiol, vol. 309, no. 5, Sept. 2015, pp. H790–803. Pubmed, doi:10.1152/ajpheart.00803.2014.
Dokun AO, Chen L, Okutsu M, Farber CR, Hazarika S, Jones WS, Craig D, Marchuk DA, Lye RJ, Shah SH, Annex BH. ADAM12: a genetic modifier of preclinical peripheral arterial disease. Am J Physiol Heart Circ Physiol. 2015 Sep;309(5):H790–H803.

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

September 2015

Volume

309

Issue

5

Start / End Page

H790 / H803

Location

United States

Related Subject Headings

  • Receptor, TIE-2
  • Peripheral Arterial Disease
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Endothelium, Vascular
  • Endothelial Cells
  • Cell Proliferation
  • Cardiovascular System & Hematology