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Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms.

Publication ,  Journal Article
Manning, MW; Cassis, LA; Daugherty, A
Published in: Arterioscler Thromb Vasc Biol
March 1, 2003

OBJECTIVE: Angiotensin II (AngII) infusion into hyperlipidemic mice leads to the rapid formation of atherosclerotic lesions and abdominal aortic aneurysms (AAAs). To define the role of matrix metalloproteinases (MMPs) in the development of these vascular pathologies, we administered the broad-spectrum MMP inhibitor doxycycline to saline- and AngII-infused LDL receptor-/- mice. METHODS AND RESULTS: Mice were placed on a high-fat diet for 1 week before infusion with either saline or AngII (1000 ng x kg(-1) x min(-1)) via osmotic pumps for 28 days. Doxycycline (30 mg x kg(-1) x d(-1)) was administered in the drinking water to both saline- and AngII-infused mice. Administration of doxycycline did not significantly influence systolic blood pressure, serum cholesterol concentrations, or lipoprotein-cholesterol distribution. Doxycycline had no effect on the extent of atherosclerosis in saline- or AngII-infused mice. In contrast, doxycycline markedly reduced the incidence of AAA formation (86% vs 35%, AngII vs AngII+doxycycline, respectively; P<0.05), in addition to reducing aneurysm severity. CONCLUSIONS: These data do not imply a role for MMPs in AngII-induced atherosclerosis but provide evidence consistent with a role in AngII-induced AAA formation.

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Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

March 1, 2003

Volume

23

Issue

3

Start / End Page

483 / 488

Location

United States

Related Subject Headings

  • Mice, Mutant Strains
  • Mice
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase Inhibitors
  • Male
  • Lipoproteins
  • Hyperlipidemias
  • Doxycycline
  • Cholesterol
  • Cardiovascular System & Hematology
 

Citation

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Manning, M. W., Cassis, L. A., & Daugherty, A. (2003). Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol, 23(3), 483–488. https://doi.org/10.1161/01.ATV.0000058404.92759.32
Manning, Michael W., Lisa A. Cassis, and Alan Daugherty. “Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms.Arterioscler Thromb Vasc Biol 23, no. 3 (March 1, 2003): 483–88. https://doi.org/10.1161/01.ATV.0000058404.92759.32.
Manning, Michael W., et al. “Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms.Arterioscler Thromb Vasc Biol, vol. 23, no. 3, Mar. 2003, pp. 483–88. Pubmed, doi:10.1161/01.ATV.0000058404.92759.32.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

March 1, 2003

Volume

23

Issue

3

Start / End Page

483 / 488

Location

United States

Related Subject Headings

  • Mice, Mutant Strains
  • Mice
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase Inhibitors
  • Male
  • Lipoproteins
  • Hyperlipidemias
  • Doxycycline
  • Cholesterol
  • Cardiovascular System & Hematology