J Korean Med Sci.  2009 Aug;24(4):596-604. 10.3346/jkms.2009.24.4.596.

Atherosclerotic Progression Attenuates the Expression of Nogo-B in Autopsied Coronary Artery: Pathology and Virtual Histology Intravascular Ultrasound Analysis

• Lee WS
• Kim SW
• Hong SA
• Lee TJ
• Park ES
• Kim HJ
• Lee KJ
• Kim TH
• Kim CJ
• Ryu WS

• KMID: 1779190
• DOI: http://doi.org/10.3346/jkms.2009.24.4.596

Abstract

The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5+/-8.3 yr), 12 late FAs (42.6+/-16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4+/-11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8+/-6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.

Keyword

Atherosclerosis; Nogo Protein; Ultrasonography, Interventional; Autopsy

MeSH Terms

Adult
Age Factors
Coronary Artery Disease/*diagnosis/pathology/ultrasonography
Coronary Vessels/*pathology/*ultrasonography
Disease Progression
Female
Humans
Male
Middle Aged
Myelin Proteins/*metabolism
Ultrasonography, Interventional

Figure

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  Fig. 1 Classification of fibroatheromas by virtual histology intravascular ultrasound. Early fibroatheromas (A) had less extensively necrotic cores (red color) and greater fibrous (green color) composition, while thick-cap fibroatheromas (C) and thin-cap fibroatheromas (D) had larger necrotic cores and more extensive calcium (white color) deposition. F, fibrous; FF, fibrofatty; NC, necrotic core; DC, dense calcium.

• 

  Fig. 2 Comparative VH-IVUS and microscopic findings between early fibroatheromas (FA) or late FAs and advanced FAs. Early FAs (A, B) had smaller necrotic cores compared to advanced FAs (F, G) with larger lipid pools. Late FAs (C) had few calcium components, while advanced FAs (H) had a large amount of calcium and decalcified empty spaces (arrows). The expression of CD68-positive macrophages (arrows) was strong in advanced FA (I) rather than in late FA (D). MMP-9 activity (arrows) was also prominent in advanced FA (J) as opposed to late FA (E). (B and G, H&E staining at ×40 magnification; C and H, von Kossa staining at ×40 and ×100 magnification, respectively; D and I, CD68 immunohistochemical staining at ×100 magnification; E and J, MMP-9 immunohistochemical staining at ×100 magnification).

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  Fig. 3 Quantitative graphs of necrotic cores, calcium, CD68-positive macrophages, and MMP-9 activity in various stages of FA.

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  Fig. 4 The correlation of necrotic core area between VH-IVUS and pathology in human autopsied coronary arteries.

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  Fig. 5 Nogo-B expression with plaque growth. Early fibroatheromas (FA) (B and F) showed diffuse Nogo-B expression (arrows) comparable to that seen in controls (A and E). Late FAs (C and G) had weaker, focal expression (arrows) of Nogo-B compared to early FAs. Advanced FA (D and H) demonstrated much weaker focal Nogo-B activity (arrows) compared to that seen in early FA or late FA. I, quantitative graphs of Nogo-B expression in various FA stages. (Immunohistochemical staining for Nogo-B, A to D, ×40 magnification, E to H, ×100 magnification).

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  Fig. 6 The correlation between immunohistochemical Nogo-B activity, and plaque composition and CD68/MMP-9 expression. Nogo-B expression carried a significant negative correlation with core necrosis (A), but not with calcification (B). Nogo-B expression had a significant negative correlation with the number of CD68-positive cells (C), but not with MMP-9 expression (D).

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