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Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis  Valdeci da Cunha, PhD, Baby Martin-McNulty,

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Presentation on theme: "Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis  Valdeci da Cunha, PhD, Baby Martin-McNulty,"— Presentation transcript:

1 Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis  Valdeci da Cunha, PhD, Baby Martin-McNulty, BS, Jon Vincelette, BS, David F. Choy, BS, We-Wei Li, PhD, Miriam Schroeder, BS, Mithra Mahmoudi, MS, Meredith Halks-Miller, MD, Dennis W. Wilson, PhD, Ronald Vergona, PhD, Mark E. Sullivan, PhD, Yi-Xin (Jim) Wang, MD  Journal of Vascular Surgery  Volume 44, Issue 2, Pages (August 2006) DOI: /j.jvs Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

2 Fig 1 Cross-sectional areas of adventitial (A), medial (B), and intimal (C) layers of ligated arteries from control and angiotensin II–treated mice. Bars represent mean ± SEM. *P < .05. Ang, Angiotensin. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

3 Fig 2 Vessel diameter (A) of ligated arteries from control and angiotensin II–treated mice and its correlation with the respective intimal area (B). Lumen diameter of ligated arteries from control and angiotensin II–treated mice (C) and its correlation with the respective intimal area (D). Bars represent the mean ± SEM, and circles represent individual measurements. *P < .05. Ang, Angiotensin. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

4 Fig 3 Cross-sectional foam cell area (A) and semiquantitative analysis of α-actin–positive (B) and MAC-3–positive (C) areas in the intima of ligated arteries from control and angiotensin II–treated mice. Bars represent the mean ± SEM. *P < .05. En face ligated carotid arteries from representative control and angiotensin II–treated mice were stained with Oil Red O (D). Ang, Angiotensin. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

5 Fig 4 Representative sections of ligated arteries from control (upper) and angiotensin II–treated (lower) mice were stained with hematoxylin and eosin and immunostained for macrophages (MAC-3) and smooth muscle cells (SMCs; α-actin). Intimal lesions were characterized by macrophage foam cells adjacent to the internal elastic lamina surrounded by proliferating SMCs. Note the larger foam cell plaque and thicker fibromuscular layer in the lesion from an angiotensin II–treated mouse. Nonfoamy macrophages were also present within SMC-rich regions in both groups. The artery from the angiotensin II–treated animal underwent significant enlargement in relation to the control, as evidenced by the stretched aspect of the elastic laminae. Such an alteration in the morphology of the elastic laminae is not an artifact of the fixation method, because it was consistently found in all vessels with large intimal areas, in agreement with previous observations.15 Additional findings in angiotensin II–treated mice included a thicker neoadventitial area. Ang, Angiotensin. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

6 Fig 5 (Upper panel) A thickened intima from a control animal displaying smooth muscle cells in a matrix background is shown (different regions of the vessel). Note the presence of rare small intralesional vessels (open arrow). (Lower panel) Advanced lesions in angiotensin II–treated mice display a more complex morphology characterized by large and more irregular intralesional vessels (marked by an open arrow) and the presence of intralesional erythrocytes (thin arrow) and hemosiderin (thick arrow), which are indicators of recent and previous hemorrhage. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

7 Fig 6 A, Quantitative determination of active matrix metalloproteinase (MMP)-2 levels in homogenates of ligated carotid arteries from control and angiotensin II–treated mice. Bars represent mean ± SEM; *P < .05. B, MMP-2 immunostaining and hematoxylin and eosin staining in representative sections of ligated carotid arteries from control and angiotensin II–treated mice. The most pronounced areas of MMP-2 localization correspond to foam cell–rich areas adjacent to the IEL, as indicated by the arrows. Ang, Angiotensin. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2006 The Society for Vascular Surgery Terms and Conditions

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