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Immunohistochemical analysis of hepatocyte growth factor in human coronary atherectomy specimens: comparison with
1Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan. hiron@mcai.med.hiroshima-u.ac.jp
Insights
Hepatocyte growth factor (HGF) is found in human coronary artery lesions, particularly in thrombotic tissue. Macrophages produce HGF, suggesting a role in thrombus-related coronary plaque formation.
Area of Science:
- Cardiovascular Biology
- Immunohistochemistry
- Molecular Medicine
Background:
- Coronary artery disease involves complex plaque formation.
- Hepatocyte growth factor/scatter factor (HGF/SF) is a key signaling molecule.
- Transforming growth factor beta (TGF-beta) isoforms are implicated in vascular remodeling.
Purpose of the Study:
- To investigate the expression and localization of HGF/SF in human coronary artery lesions.
- To compare HGF/SF localization with TGF-beta isoforms.
- To elucidate the cellular sources of HGF/SF in atherosclerotic plaques.
Main Methods:
- Immunohistochemistry was used to detect HGF/SF and TGF-beta isoforms.
- 59 human coronary artery lesions from directional coronary atherectomy were analyzed.
- Control coronary arteries from autopsy were used for comparison.
Main Results:
- HGF-like immunoreactivity (HGF-IR) was detected in 35.6% of specimens.
- HGF immunopositivity was significantly higher in thrombotic tissue (45%) compared to fibrous tissue, neointimal hyperplasia, and atheromatous gruel.
- HGF-IR was primarily observed in inflammatory cells (monocytes/macrophages), especially in thrombotic areas, and weakly in smooth muscle cells (SMCs).
- In control arteries, HGF-IR was strongly expressed in SMCs.
Conclusions:
- HGF produced by macrophages plays a role in thrombus-associated coronary plaque formation.
- The cellular source of HGF differs between atherosclerotic lesions and healthy coronary arteries.
- HGF localization suggests involvement in the inflammatory processes within coronary plaques.
Abstract:
The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.