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Drebrin regulates angiotensin II-induced aortic remodelling.

Publication ,  Journal Article
Zhang, L; Wu, J-H; Huang, T-Q; Nepliouev, I; Brian, L; Zhang, Z; Wertman, V; Rudemiller, NP; McMahon, TJ; Shenoy, SK; Miller, FJ; Crowley, SD ...
Published in: Cardiovasc Res
November 1, 2018

AIMS: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebrin inhibits angiotensin II-induced remodelling of the proximal aorta. METHODS AND RESULTS: Angiotensin II was administered via osmotic minipumps at 1000 ng/kg/min continuously for 28 days in SM22-Cre+/Dbnflox/flox (SMC-Dbn-/-) and control mice. Blood pressure responses to angiotensin II were assessed by telemetry. After angiotensin II infusion, we assessed remodelling in the proximal ascending aorta by echocardiography and planimetry of histological cross sections. Although the degree of hypertension was equivalent in SMC-Dbn-/- and control mice, SMC-Dbn-/- mice nonetheless exhibited 60% more proximal aortic medial thickening and two-fold more outward aortic remodelling than control mice in response to angiotensin II. Proximal aortas demonstrated greater cellular proliferation and matrix deposition in SMC-Dbn-/- mice than in control mice, as evidenced by a higher prevalence of proliferating cell nuclear antigen-positive nuclei and higher levels of collagen I. Compared with control mouse aortas, SMC-Dbn-/- aortas demonstrated greater angiotensin II-induced NADPH oxidase activation and inflammation, evidenced by higher levels of Ser-536-phosphorylated NFκB p65 subunits and higher levels of vascular cell adhesion molecule-1, matrix metalloproteinase-9, and adventitial macrophages. CONCLUSIONS: We conclude that SMC Drebrin deficiency augments angiotensin II-induced inflammation and adverse aortic remodelling.

Duke Scholars

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Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

November 1, 2018

Volume

114

Issue

13

Start / End Page

1806 / 1815

Location

England

Related Subject Headings

  • Vascular Remodeling
  • Signal Transduction
  • Reactive Oxygen Species
  • Neuropeptides
  • NADPH Oxidases
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Inflammation Mediators
 

Citation

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Zhang, L., Wu, J.-H., Huang, T.-Q., Nepliouev, I., Brian, L., Zhang, Z., … Stiber, J. A. (2018). Drebrin regulates angiotensin II-induced aortic remodelling. Cardiovasc Res, 114(13), 1806–1815. https://doi.org/10.1093/cvr/cvy151
Zhang, Lisheng, Jiao-Hui Wu, Tai-Qin Huang, Igor Nepliouev, Leigh Brian, Zhushan Zhang, Virginia Wertman, et al. “Drebrin regulates angiotensin II-induced aortic remodelling.Cardiovasc Res 114, no. 13 (November 1, 2018): 1806–15. https://doi.org/10.1093/cvr/cvy151.
Zhang L, Wu J-H, Huang T-Q, Nepliouev I, Brian L, Zhang Z, et al. Drebrin regulates angiotensin II-induced aortic remodelling. Cardiovasc Res. 2018 Nov 1;114(13):1806–15.
Zhang, Lisheng, et al. “Drebrin regulates angiotensin II-induced aortic remodelling.Cardiovasc Res, vol. 114, no. 13, Nov. 2018, pp. 1806–15. Pubmed, doi:10.1093/cvr/cvy151.
Zhang L, Wu J-H, Huang T-Q, Nepliouev I, Brian L, Zhang Z, Wertman V, Rudemiller NP, McMahon TJ, Shenoy SK, Miller FJ, Crowley SD, Freedman NJ, Stiber JA. Drebrin regulates angiotensin II-induced aortic remodelling. Cardiovasc Res. 2018 Nov 1;114(13):1806–1815.
Journal cover image

Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

November 1, 2018

Volume

114

Issue

13

Start / End Page

1806 / 1815

Location

England

Related Subject Headings

  • Vascular Remodeling
  • Signal Transduction
  • Reactive Oxygen Species
  • Neuropeptides
  • NADPH Oxidases
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Inflammation Mediators