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

Michael W. Manning, Lisa A. Cassis, Alan Daugherty

Research output: Contribution to journalArticlepeer-review

271 Scopus citations

Abstract

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 · kg-1 · min-1) via osmotic pumps for 28 days. Doxycycline (30 mg · kg-1 · 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.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number3
DOIs
StatePublished - Mar 1 2003

Keywords

  • Aneurysms
  • Angiotensin
  • Atherosclerosis
  • Doxycycline
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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