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Immunolocalisation of fibrin in coronary atherosclerosis: implications for necrotic core development
Fabio Tavora1, Nathaniel Cresswell, Ling Li
1Armed Forces Institute of Pathology, Washington, DC, USA.
Insights
Fibrin accumulates in atherosclerotic plaque cores before red blood cells appear, indicating early vessel leakage. This fibrin may bridge the gap between pre-atheroma and advanced atheroma development.
Area of Science:
- Cardiovascular Pathology
- Atherosclerosis Research
- Immunohistochemistry
Background:
- Intraplaque hemorrhage is linked to necrotic core expansion in atherosclerotic plaques.
- The role of fibrin in different stages of plaque progression requires further investigation.
Purpose of the Study:
- To investigate the presence and localization of fibrin within human coronary artery plaques across various stages of development.
- To correlate fibrin deposition with intraplaque neovascularization and red blood cell breakdown.
Main Methods:
- Human coronary artery sections (n=74) were analyzed using immunohistochemistry for fibrin II, glycophorin A (red blood cell marker), and CD31 (endothelial marker).
- Plaques were categorized into distinct American Heart Association (AHA) grades, including adaptive intimal thickening (AIT), intimal xanthomas, pathologic intimal thickening (PIT), fibroatheromas (FA), and thin cap fibroatheromas (TCFA).
Main Results:
- Fibrin was largely absent in early plaque stages (AIT, PIT) but present in early fibroatheroma cores.
- Late fibroatheromas and thin cap fibroatheromas showed significant intracore fibrin deposition.
- Intimal vasa vasorum counts correlated positively with fibrin scores, with minimal red cell breakdown observed in many fibrin-positive cores.
Conclusions:
- Fibrin deposition in necrotic cores is associated with increased intraplaque vasa vasorum and precedes overt intraplaque hemorrhage.
- Fibrin may contribute to the transition from pre-atheroma to advanced atheroma stages.
Background:
Intraplaque haemorrhage has been shown to be important in necrotic core enlargement. Immunolocalisation of fibrin within progressive stages of plaque progression has not been extensively studied.
Methods:
Histological sections (n = 74) of human coronary arteries were stained immunohistochemically for fibrin II, red blood cell antigen (glycophorin A), and CD31. Plaques were chosen to represent a range of lesions [6 adaptive intimal thickening, AIT (AHA grade I); 4 intimal xanthomas (AHA grade II), 19 pathologic intimal thickening, PIT (AHA grade III, or pre-atheroma); 34 fibroatheromas, FA (AHA grade IV and V); and 11 thin cap fibroatheromas (TCFA, AHA grade IV)].
Results:
Fibrin was generally absent in the intima of AIT and PIT, with moderate staining in cores of early FA (2.6 +/- 0.3). All late FA and TCFA demonstrated intracore fibrin, with mean scores of 2.9 +/- 0.3 and 3.0 +/- 0.3, respectively. Intimal vasa vasorum counts increased with intimal fibrin score (p < 0.0001); in 68% of cores with fibrin staining, there was minimal or no evidence of red cell breakdown.
Conclusions:
Fibrin in necrotic cores is present proportional to intraplaque vasa vasorum and before red cells, suggesting leakage of vessels before frank intraplaque haemorrhage. Fibrin may play a role in the bridge between pre-atheroma and atheroma.
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