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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

Observation of autophagy in unstable atherosclerotic plaque via transmission electron microscopy (TEM). Autophagic vacuoles with myelin structures (arrows) (a-b) and autophagic vacuoles with organelle inclusions (arrows) (c) were detectable in the cytoplasm of SMCs in the media adjacent to intima. Myelin structures were detectable in macrophages in fibrous cap and shoulder of plaque (d-e). The formation of autophagolysosomes was detected in endothelial cells (ECs) (f). Scale bars=2 μm.
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Figure 2: Observation of autophagy in unstable atherosclerotic plaque via transmission electron microscopy (TEM). Autophagic vacuoles with myelin structures (arrows) (a-b) and autophagic vacuoles with organelle inclusions (arrows) (c) were detectable in the cytoplasm of SMCs in the media adjacent to intima. Myelin structures were detectable in macrophages in fibrous cap and shoulder of plaque (d-e). The formation of autophagolysosomes was detected in endothelial cells (ECs) (f). Scale bars=2 μm.

Mentions: We observed the typical ultrastructural features of autophagy via TEM, such as vacuolization and formation of myelin figures in the nuclei of SMCs and macrophages [Figures 2a–e]. However, no abnormal chromatin aggregation was found in the nuclei of SMCs [Figures 2a–c] and macrophages [Figure 2d and e]. In ECs [Figure 2f], autophagolysosome was also found.


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)

Observation of autophagy in unstable atherosclerotic plaque via transmission electron microscopy (TEM). Autophagic vacuoles with myelin structures (arrows) (a-b) and autophagic vacuoles with organelle inclusions (arrows) (c) were detectable in the cytoplasm of SMCs in the media adjacent to intima. Myelin structures were detectable in macrophages in fibrous cap and shoulder of plaque (d-e). The formation of autophagolysosomes was detected in endothelial cells (ECs) (f). Scale bars=2 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Observation of autophagy in unstable atherosclerotic plaque via transmission electron microscopy (TEM). Autophagic vacuoles with myelin structures (arrows) (a-b) and autophagic vacuoles with organelle inclusions (arrows) (c) were detectable in the cytoplasm of SMCs in the media adjacent to intima. Myelin structures were detectable in macrophages in fibrous cap and shoulder of plaque (d-e). The formation of autophagolysosomes was detected in endothelial cells (ECs) (f). Scale bars=2 μm.
Mentions: We observed the typical ultrastructural features of autophagy via TEM, such as vacuolization and formation of myelin figures in the nuclei of SMCs and macrophages [Figures 2a–e]. However, no abnormal chromatin aggregation was found in the nuclei of SMCs [Figures 2a–c] and macrophages [Figure 2d and e]. In ECs [Figure 2f], autophagolysosome was also found.

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