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Autophagy in atherosclerosis: a phenomenon found in human carotid atherosclerotic plaques.

Liu H, Cao Y, Tong T, Shi J, Zhang Y, Yang Y, Liu C - Chin. Med. J. (2015)

Bottom Line: Autophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques.In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol.These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.

ABSTRACT

Background: Autophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques. Here, we investigated autophagy in smooth muscle cells (SMCs), endothelial cells (ECs), and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM), western blotting, and immunohistochemistry analysis.

Methods: The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining. The ultrastructural morphology of the SMCs, ECs, and macrophages in these plaques was observed via TEM. The localization of microtubule-associated protein 1 light chain 3 (MAP1-LC3), a relatively special maker of autophagy, in plaques was observed by double fluorescent immunochemistry and western blotting.

Results: All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation. By double fluorescent immunochemistry, the expression of LC3-II increased in the SMCs of the fibrous cap, the macrophages, and the microvascular ECs of the plaque shoulders. The protein level of LC3-II by western blotting significantly increased in plaques compared with normal controls. In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol. These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques.

Conclusions: Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods, which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

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Related in: MedlinePlus

Macroscopic and histological observation of unstable atherosclerotic plaque. (a) Plaque specimen taken by carotid endarterectomy (CEA) shows composite secondary lesions, such as intima erosion, ulcerasion, or hemorrhage. (b-d) Hematoxylin and eosin (H and E) staining: (b) Gross histological observation of plaque showed lipid-laden foam cells in intima (arrows). (c) Smooth muscle cells (SMCs) of the media adjacent to intima lesion were disarranged and proliferated (arrows). (d) Histological observation of normal carotid artery showed smooth intima, regularly arranged SMCs and integrity of adventitia.
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Figure 1: Macroscopic and histological observation of unstable atherosclerotic plaque. (a) Plaque specimen taken by carotid endarterectomy (CEA) shows composite secondary lesions, such as intima erosion, ulcerasion, or hemorrhage. (b-d) Hematoxylin and eosin (H and E) staining: (b) Gross histological observation of plaque showed lipid-laden foam cells in intima (arrows). (c) Smooth muscle cells (SMCs) of the media adjacent to intima lesion were disarranged and proliferated (arrows). (d) Histological observation of normal carotid artery showed smooth intima, regularly arranged SMCs and integrity of adventitia.

Mentions: The surfaces of all plaque samples were humped. Yellow atherosclerotic lipid deposition was found in subintim of all samples. Some samples showed composite secondary lesions, such as intima erosion, ulcerarions, or hemorrhage [Figure 1a]. In contrast, normal control showed smooth and flat intima with significant wall tension.


Autophagy in atherosclerosis: a phenomenon found in human carotid atherosclerotic plaques.

Liu H, Cao Y, Tong T, Shi J, Zhang Y, Yang Y, Liu C - Chin. Med. J. (2015)

Macroscopic and histological observation of unstable atherosclerotic plaque. (a) Plaque specimen taken by carotid endarterectomy (CEA) shows composite secondary lesions, such as intima erosion, ulcerasion, or hemorrhage. (b-d) Hematoxylin and eosin (H and E) staining: (b) Gross histological observation of plaque showed lipid-laden foam cells in intima (arrows). (c) Smooth muscle cells (SMCs) of the media adjacent to intima lesion were disarranged and proliferated (arrows). (d) Histological observation of normal carotid artery showed smooth intima, regularly arranged SMCs and integrity of adventitia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837822&req=5

Figure 1: Macroscopic and histological observation of unstable atherosclerotic plaque. (a) Plaque specimen taken by carotid endarterectomy (CEA) shows composite secondary lesions, such as intima erosion, ulcerasion, or hemorrhage. (b-d) Hematoxylin and eosin (H and E) staining: (b) Gross histological observation of plaque showed lipid-laden foam cells in intima (arrows). (c) Smooth muscle cells (SMCs) of the media adjacent to intima lesion were disarranged and proliferated (arrows). (d) Histological observation of normal carotid artery showed smooth intima, regularly arranged SMCs and integrity of adventitia.
Mentions: The surfaces of all plaque samples were humped. Yellow atherosclerotic lipid deposition was found in subintim of all samples. Some samples showed composite secondary lesions, such as intima erosion, ulcerarions, or hemorrhage [Figure 1a]. In contrast, normal control showed smooth and flat intima with significant wall tension.

Bottom Line: Autophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques.In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol.These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.

ABSTRACT

Background: Autophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques. Here, we investigated autophagy in smooth muscle cells (SMCs), endothelial cells (ECs), and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM), western blotting, and immunohistochemistry analysis.

Methods: The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining. The ultrastructural morphology of the SMCs, ECs, and macrophages in these plaques was observed via TEM. The localization of microtubule-associated protein 1 light chain 3 (MAP1-LC3), a relatively special maker of autophagy, in plaques was observed by double fluorescent immunochemistry and western blotting.

Results: All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation. By double fluorescent immunochemistry, the expression of LC3-II increased in the SMCs of the fibrous cap, the macrophages, and the microvascular ECs of the plaque shoulders. The protein level of LC3-II by western blotting significantly increased in plaques compared with normal controls. In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol. These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques.

Conclusions: Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods, which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

Show MeSH
Related in: MedlinePlus