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Analysis of in situ and ex vivo αVβ3 integrin expression during experimental carotid atherogenesis.

Yao Y, Jiang Y, Sheng Z, Zhang Y, An Y, Yan F, Ma G, Liu N, Teng G, Cheng Z - Int J Nanomedicine (2012)

Bottom Line: Immunostaining confirmed the presence of mural α(V)β(3) integrin expression in macrophages in the neointima.Signal intensity increased in a macrophage density-dependent fashion in the stenotic segments.This expression can estimate the macrophage-bound inflammatory activity of atherosclerotic lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People's Republic of China.

ABSTRACT

Objective: Mural inflammation has been shown to contribute to the development of plaque, with the α(V)β(3) integrin highly expressed in atherosclerotic plaques. We herein examined α(V)β(3) integrin expression as a function of carotid atherosclerosis formation in the apolipoprotein E-deficient (apoE(-/-)) mouse.

Methods and results: Constrictive collars were placed around the left common carotid arteries of apo E(-/-) mice maintained on a high-fat diet (n = 14). Before and 21 days following collar placement, in vivo serial magnetic resonance imaging (MRI) measurements of the carotid aortic diameter were performed using a 7T magnetic resonance (MR) scanner. Near- infrared fluorescence (NIRF) imaging was performed (n = 6) using an in vivo imaging system 0-24 hours following administration of 1.0 nmol c(RGDyK)-Cy5.5 via the tail vein. A competition experiment was performed by the co-injection of a saturating dose of bicyclic RGD peptide H-Glu[cyclo(Arg-Gly-Asp-D-Tyr-Lys)]2 (n = 3). Following image acquisition and sacrifice at 24 hours after injection, carotid arteries were harvested for histological analyses. Neointima formation and arterial remodeling in the carotid arteries of apoE(-/-) mice were induced by the placement of a constrictive collar. Significantly greater fluorescent signals were obtained from constrictive collar left common carotid arteries as compared to uninvolved aortic segments in constrictive collar mice. Binding to stenotic lesions was efficiently blocked in competition experiments. Immunostaining confirmed the presence of mural α(V)β(3) integrin expression in macrophages in the neointima. Signal intensity increased in a macrophage density-dependent fashion in the stenotic segments.

Conclusion: Mural α(V)β(3) integrin expression, as determined using RGD-Cy5.5 near-infrared optical imaging, was increased in carotid arteries with constrictive collars in experimental mice. This expression can estimate the macrophage-bound inflammatory activity of atherosclerotic lesions.

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Identification of neointima formation in apoE−/− mouse using in vivo MRI and the corresponding histology. (A) Example of MR images at day 10 following perivascular collar placement. MRI of a mouse with slight stenosis of the left carotid artery. The image shows an in vivo image of a transverse section at the RCA and LCA after perivascular collar placement using MSME proton-density/T2-weighted sequences. (B) Example of MR images at day 21 following perivascular collar placement. MRI of a mouse with significant stenosis of the left carotid artery. LCA with a neointima formation reveals a stenostic lumen, white arrows indicate aortic stenosis. (C) Corresponding H&E stain obtained in a mouse at 21 days following perivascular collar placement. Representative photomicrographs showing hematoxylin and eosin stained cross sections of proximal carotid site (H&E staining, 20×). (D) Representative carotid artery tree image in mice acquired at 7 T using 3D-FLASH sequence. The longitudinal view shows the characteristic stenosis of the left carotid artery.Abbreviations: H&E, hematoxylin-and-eosin; LCA, left carotid artery; MR, magnetic resonance; MRI, magnetic resonance imaging; MSME, multi-spin multi-echo; RCA, right carotid artery.
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f2-ijn-7-641: Identification of neointima formation in apoE−/− mouse using in vivo MRI and the corresponding histology. (A) Example of MR images at day 10 following perivascular collar placement. MRI of a mouse with slight stenosis of the left carotid artery. The image shows an in vivo image of a transverse section at the RCA and LCA after perivascular collar placement using MSME proton-density/T2-weighted sequences. (B) Example of MR images at day 21 following perivascular collar placement. MRI of a mouse with significant stenosis of the left carotid artery. LCA with a neointima formation reveals a stenostic lumen, white arrows indicate aortic stenosis. (C) Corresponding H&E stain obtained in a mouse at 21 days following perivascular collar placement. Representative photomicrographs showing hematoxylin and eosin stained cross sections of proximal carotid site (H&E staining, 20×). (D) Representative carotid artery tree image in mice acquired at 7 T using 3D-FLASH sequence. The longitudinal view shows the characteristic stenosis of the left carotid artery.Abbreviations: H&E, hematoxylin-and-eosin; LCA, left carotid artery; MR, magnetic resonance; MRI, magnetic resonance imaging; MSME, multi-spin multi-echo; RCA, right carotid artery.

Mentions: The significant lumen changes observed were monitored using 7.0T micro-MRI. There was a progressive stenosis of the left common carotid artery at 21 days following surgery (Figure 2).


Analysis of in situ and ex vivo αVβ3 integrin expression during experimental carotid atherogenesis.

Yao Y, Jiang Y, Sheng Z, Zhang Y, An Y, Yan F, Ma G, Liu N, Teng G, Cheng Z - Int J Nanomedicine (2012)

Identification of neointima formation in apoE−/− mouse using in vivo MRI and the corresponding histology. (A) Example of MR images at day 10 following perivascular collar placement. MRI of a mouse with slight stenosis of the left carotid artery. The image shows an in vivo image of a transverse section at the RCA and LCA after perivascular collar placement using MSME proton-density/T2-weighted sequences. (B) Example of MR images at day 21 following perivascular collar placement. MRI of a mouse with significant stenosis of the left carotid artery. LCA with a neointima formation reveals a stenostic lumen, white arrows indicate aortic stenosis. (C) Corresponding H&E stain obtained in a mouse at 21 days following perivascular collar placement. Representative photomicrographs showing hematoxylin and eosin stained cross sections of proximal carotid site (H&E staining, 20×). (D) Representative carotid artery tree image in mice acquired at 7 T using 3D-FLASH sequence. The longitudinal view shows the characteristic stenosis of the left carotid artery.Abbreviations: H&E, hematoxylin-and-eosin; LCA, left carotid artery; MR, magnetic resonance; MRI, magnetic resonance imaging; MSME, multi-spin multi-echo; RCA, right carotid artery.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3278228&req=5

f2-ijn-7-641: Identification of neointima formation in apoE−/− mouse using in vivo MRI and the corresponding histology. (A) Example of MR images at day 10 following perivascular collar placement. MRI of a mouse with slight stenosis of the left carotid artery. The image shows an in vivo image of a transverse section at the RCA and LCA after perivascular collar placement using MSME proton-density/T2-weighted sequences. (B) Example of MR images at day 21 following perivascular collar placement. MRI of a mouse with significant stenosis of the left carotid artery. LCA with a neointima formation reveals a stenostic lumen, white arrows indicate aortic stenosis. (C) Corresponding H&E stain obtained in a mouse at 21 days following perivascular collar placement. Representative photomicrographs showing hematoxylin and eosin stained cross sections of proximal carotid site (H&E staining, 20×). (D) Representative carotid artery tree image in mice acquired at 7 T using 3D-FLASH sequence. The longitudinal view shows the characteristic stenosis of the left carotid artery.Abbreviations: H&E, hematoxylin-and-eosin; LCA, left carotid artery; MR, magnetic resonance; MRI, magnetic resonance imaging; MSME, multi-spin multi-echo; RCA, right carotid artery.
Mentions: The significant lumen changes observed were monitored using 7.0T micro-MRI. There was a progressive stenosis of the left common carotid artery at 21 days following surgery (Figure 2).

Bottom Line: Immunostaining confirmed the presence of mural α(V)β(3) integrin expression in macrophages in the neointima.Signal intensity increased in a macrophage density-dependent fashion in the stenotic segments.This expression can estimate the macrophage-bound inflammatory activity of atherosclerotic lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People's Republic of China.

ABSTRACT

Objective: Mural inflammation has been shown to contribute to the development of plaque, with the α(V)β(3) integrin highly expressed in atherosclerotic plaques. We herein examined α(V)β(3) integrin expression as a function of carotid atherosclerosis formation in the apolipoprotein E-deficient (apoE(-/-)) mouse.

Methods and results: Constrictive collars were placed around the left common carotid arteries of apo E(-/-) mice maintained on a high-fat diet (n = 14). Before and 21 days following collar placement, in vivo serial magnetic resonance imaging (MRI) measurements of the carotid aortic diameter were performed using a 7T magnetic resonance (MR) scanner. Near- infrared fluorescence (NIRF) imaging was performed (n = 6) using an in vivo imaging system 0-24 hours following administration of 1.0 nmol c(RGDyK)-Cy5.5 via the tail vein. A competition experiment was performed by the co-injection of a saturating dose of bicyclic RGD peptide H-Glu[cyclo(Arg-Gly-Asp-D-Tyr-Lys)]2 (n = 3). Following image acquisition and sacrifice at 24 hours after injection, carotid arteries were harvested for histological analyses. Neointima formation and arterial remodeling in the carotid arteries of apoE(-/-) mice were induced by the placement of a constrictive collar. Significantly greater fluorescent signals were obtained from constrictive collar left common carotid arteries as compared to uninvolved aortic segments in constrictive collar mice. Binding to stenotic lesions was efficiently blocked in competition experiments. Immunostaining confirmed the presence of mural α(V)β(3) integrin expression in macrophages in the neointima. Signal intensity increased in a macrophage density-dependent fashion in the stenotic segments.

Conclusion: Mural α(V)β(3) integrin expression, as determined using RGD-Cy5.5 near-infrared optical imaging, was increased in carotid arteries with constrictive collars in experimental mice. This expression can estimate the macrophage-bound inflammatory activity of atherosclerotic lesions.

Show MeSH
Related in: MedlinePlus