Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Fei Huang, Joel C. Thompson, Patricia G. Wilson, Hnin H. Aung, John C Rutledge, Lisa R. Tannock

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Angiotensin II (angII) is known to promote atherosclerosis; however, the mechanisms involved are not fully understood. To determine whether angII stimulates proteoglycan production and LDL retention, LDL receptor-deficient mice were infused with angII (1,000 ng/kg/min) or saline via osmotic minipumps. To control for the hypertensive effect of angII, a parallel group received norepinephrine (NE; 5.6 mg/kg/day). Arterial lipid accumulation was evaluated by measuring the retention rate of LDL in isolated carotid arteries perfused ex vivo. Mice infused with angII had increased vascular content of biglycan and perlecan and retained twice as much LDL as saline- or NE-infused mice, although no group developed atherosclerosis at this time. To determine whether this increase in biglycan and perlecan content predisposed to atherosclerosis development, mice were infused with angII, saline, or NE for 4 weeks, then pumps were removed and mice received an atherogenic Western diet for another 6 weeks. Mice that had received angII infusions had 3-fold increased atherosclerosis compared with mice that had received saline or NE, and apolipoprotein B colocalized with both proteoglycans. Thus, one mechanism by which angII promotes atherosclerosis is increased proteoglycan synthesis and increased arterial LDL retention, which precedes and contributes to atherosclerosis development.

Original languageEnglish (US)
Pages (from-to)521-530
Number of pages10
JournalJournal of Lipid Research
Volume49
Issue number3
DOIs
StatePublished - Mar 1 2008

Fingerprint

Proteoglycans
Angiotensin II
Blood Vessels
Atherosclerosis
Biglycan
Atherogenic Diet
LDL Receptors
Apolipoproteins B
Nutrition
Carotid Arteries
Norepinephrine
Pumps
Lipids
oxidized low density lipoprotein

Keywords

  • Biglycan
  • Extracellular matrix
  • Low density lipoprotein retention
  • Norepinephrine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development. / Huang, Fei; Thompson, Joel C.; Wilson, Patricia G.; Aung, Hnin H.; Rutledge, John C; Tannock, Lisa R.

In: Journal of Lipid Research, Vol. 49, No. 3, 01.03.2008, p. 521-530.

Research output: Contribution to journalArticle

Huang, Fei ; Thompson, Joel C. ; Wilson, Patricia G. ; Aung, Hnin H. ; Rutledge, John C ; Tannock, Lisa R. / Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development. In: Journal of Lipid Research. 2008 ; Vol. 49, No. 3. pp. 521-530.
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