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[Cardiovascular pathology of Marfan syndrome]
1Division of Surgical Pathology, Nippon Medical School Hospital, Tokyo, Japan.
Abstract:
In Marfan syndrome, mutations of the fibrillin gene lead to various cardiovascular lesions, such as aortic root dilatation, aortic dissection, and floppy mitral or aortic valve. Disorganization and fragmentation of elastic fibers, characteristic histologic findings of cardiac valves and aortas in Marfan syndrome, are similar to the changes of elastic fibers in non-Marfan dissected aortas and idiopathic floppy valves. Immunohistochemical study using antielastin antibody showed even and diffuse staining pattern in finely disrupted elastic fibers, which could result from either immaturity and incomplete cross-linking or proteolytic damage. Ultrastructurally, decrease of the microfibrils and round-shaped expansion of the amorphous components of elastic fibers were observed. These features, resembled those of the elastic fibers in animals treated with inhibitor of lysyl oxidase, suggest the abnormality of elastogenesis in Marfan syndrome. Recently, the changes in the activity of the matrix metalloproteinases are thought to be responsible for the damage to the elastic fibers in Marfan syndrome. However, these changes are also found in the idiopathic floppy valves. Further investigations are necessary to distinguish the pathogenesis between idiopathic cardiovascular disorders and cardiovascular lesions in Marfan syndrome.
Insights
Marfan syndrome involves fibrillin gene mutations causing cardiovascular issues. Elastic fiber abnormalities in Marfan syndrome patients resemble those in non-Marfan conditions, suggesting shared or overlapping pathogenetic mechanisms.
Area of Science:
- Cardiovascular Pathology
- Genetics
- Connective Tissue Disorders
Background:
- Marfan syndrome, caused by fibrillin gene mutations, leads to cardiovascular complications like aortic root dilatation and valve issues.
- Histologic findings in Marfan syndrome include disorganized and fragmented elastic fibers in the aorta and cardiac valves.
- These changes are similar to those observed in non-Marfan dissected aortas and idiopathic floppy valves.
Purpose of the Study:
- To investigate the structural and functional characteristics of elastic fibers in Marfan syndrome.
- To compare elastic fiber alterations in Marfan syndrome with those in other cardiovascular conditions.
- To explore the potential role of elastogenesis and matrix metalloproteinases in Marfan syndrome pathogenesis.
Main Methods:
- Immunohistochemical analysis using antielastin antibody.
- Ultrastructural examination of elastic fibers.
- Comparison with elastic fiber changes in animal models and idiopathic cardiovascular disorders.
Main Results:
- Immunohistochemistry revealed even, diffuse staining in disrupted elastic fibers, suggesting immaturity or proteolytic damage.
- Ultrastructural analysis showed decreased microfibrils and expanded amorphous components of elastic fibers.
- Elastic fiber abnormalities in Marfan syndrome share similarities with non-Marfan dissected aortas and idiopathic floppy valves.
Conclusions:
- Elastic fiber abnormalities in Marfan syndrome may stem from impaired elastogenesis.
- Similarities in elastic fiber damage and matrix metalloproteinase activity between Marfan syndrome and idiopathic conditions complicate etiological distinction.
- Further research is needed to differentiate the pathogenesis of cardiovascular lesions in Marfan syndrome versus idiopathic disorders.