Abstract
Background: We explored the role of angiotensin II in determining the histomorphometric features of plaque stability in apolipoprotein E-deficient mice submitted to ligation of the carotid artery. Methods: Six-month-old apolipoprotein E-deficient mice underwent ligation of the common left carotid artery and were immediately assigned to receive either angiotensin II (1.4 mg · kg-1 · d-1 subcutaneously) or vehicle (phosphate-buffered saline; control) via a subcutaneous osmotic minipump for 4 weeks. Results: Ligated arteries from control animals developed intimal lesions composed of macrophage foam cell plaques, which accumulated adjacent to the internal elastic lamina and were surrounded by a fibromuscular layer. Angiotensin II-treated mice had a greater intimal area (threefold), which was accompanied by a fivefold increase in the foam cell area. Lesions from angiotensin II-treated mice also displayed complex morphology characterized by intralesional neovasculature and hemorrhage. The content of active matrix metalloproteinase 2, mainly colocalized with macrophage foam cells, and the production of the inflammatory mediators monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 were also increased by angiotensin II treatment. Although angiotensin II induced vessel expansion and lumen loss to a similar extent, only vessel enlargement correlated with intimal area. Conclusions: Taken together, this study's results support a role of angiotensin II in plaque vulnerability by promoting intraplaque neovascularization/hemorrhage, inflammation, and expansive remodeling.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 364-371 |
| Number of pages | 8 |
| Journal | Journal of Vascular Surgery |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2006 |
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ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Surgery
Cite this
Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis. / da Cunha, Valdeci; Martin-McNulty, Baby; Vincelette, Jon; Choy, David F.; Li, We Wei; Schroeder, Miriam; Mahmoudi, Mithra; Halks-Miller, Meredith; Wilson, Dennis W; Vergona, Ronald; Sullivan, Mark E.; Wang, Yi Xin (Jim).
In: Journal of Vascular Surgery, Vol. 44, No. 2, 08.2006, p. 364-371.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis
AU - da Cunha, Valdeci
AU - Martin-McNulty, Baby
AU - Vincelette, Jon
AU - Choy, David F.
AU - Li, We Wei
AU - Schroeder, Miriam
AU - Mahmoudi, Mithra
AU - Halks-Miller, Meredith
AU - Wilson, Dennis W
AU - Vergona, Ronald
AU - Sullivan, Mark E.
AU - Wang, Yi Xin (Jim)
PY - 2006/8
Y1 - 2006/8
N2 - Background: We explored the role of angiotensin II in determining the histomorphometric features of plaque stability in apolipoprotein E-deficient mice submitted to ligation of the carotid artery. Methods: Six-month-old apolipoprotein E-deficient mice underwent ligation of the common left carotid artery and were immediately assigned to receive either angiotensin II (1.4 mg · kg-1 · d-1 subcutaneously) or vehicle (phosphate-buffered saline; control) via a subcutaneous osmotic minipump for 4 weeks. Results: Ligated arteries from control animals developed intimal lesions composed of macrophage foam cell plaques, which accumulated adjacent to the internal elastic lamina and were surrounded by a fibromuscular layer. Angiotensin II-treated mice had a greater intimal area (threefold), which was accompanied by a fivefold increase in the foam cell area. Lesions from angiotensin II-treated mice also displayed complex morphology characterized by intralesional neovasculature and hemorrhage. The content of active matrix metalloproteinase 2, mainly colocalized with macrophage foam cells, and the production of the inflammatory mediators monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 were also increased by angiotensin II treatment. Although angiotensin II induced vessel expansion and lumen loss to a similar extent, only vessel enlargement correlated with intimal area. Conclusions: Taken together, this study's results support a role of angiotensin II in plaque vulnerability by promoting intraplaque neovascularization/hemorrhage, inflammation, and expansive remodeling.
AB - Background: We explored the role of angiotensin II in determining the histomorphometric features of plaque stability in apolipoprotein E-deficient mice submitted to ligation of the carotid artery. Methods: Six-month-old apolipoprotein E-deficient mice underwent ligation of the common left carotid artery and were immediately assigned to receive either angiotensin II (1.4 mg · kg-1 · d-1 subcutaneously) or vehicle (phosphate-buffered saline; control) via a subcutaneous osmotic minipump for 4 weeks. Results: Ligated arteries from control animals developed intimal lesions composed of macrophage foam cell plaques, which accumulated adjacent to the internal elastic lamina and were surrounded by a fibromuscular layer. Angiotensin II-treated mice had a greater intimal area (threefold), which was accompanied by a fivefold increase in the foam cell area. Lesions from angiotensin II-treated mice also displayed complex morphology characterized by intralesional neovasculature and hemorrhage. The content of active matrix metalloproteinase 2, mainly colocalized with macrophage foam cells, and the production of the inflammatory mediators monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 were also increased by angiotensin II treatment. Although angiotensin II induced vessel expansion and lumen loss to a similar extent, only vessel enlargement correlated with intimal area. Conclusions: Taken together, this study's results support a role of angiotensin II in plaque vulnerability by promoting intraplaque neovascularization/hemorrhage, inflammation, and expansive remodeling.
UR - http://www.scopus.com/inward/record.url?scp=33746494065&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746494065&partnerID=8YFLogxK
U2 - 10.1016/j.jvs.2006.04.033
DO - 10.1016/j.jvs.2006.04.033
M3 - Article
C2 - 16890870
AN - SCOPUS:33746494065
VL - 44
SP - 364
EP - 371
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
SN - 0741-5214
IS - 2
ER -