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Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan's syndrome
K J Fleischer1, H C Nousari, G J Anhalt
1Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Background:
Molecular defects in the glycoprotein fibrillin are believed to be responsible for impaired structural integrity of cardiovascular, skeletal, and ocular tissues in Marfan's syndrome (MFS). Traditionally, excellent results have been achieved with the Bentall composite graft repair of aneurysms of the ascending aorta in MFS. However, because of the potential complications associated with prosthetic valves, there is growing interest in techniques that preserve the native aortic valve.
Methods:
Between May 1994 and February 1995, 15 patients with a history of concomitant or remote aortic root aneurysms or dissection underwent operation for valvular heart disease. Specimens of aortic valve, ascending aortic wall, and mitral valve were obtained specifically to observe differences in fibrillin content and architecture between patients with (n = 9) and without (n = 6) MFS. In addition, control specimens of aortic valve, aortic wall, and mitral valve were obtained from 4 patients with isolated valvular or coronary artery disease but no evidence of connective tissue disorders or other aortic pathologic conditions. Fibrillin immunostaining using indirect immunofluorescence was used. Specimens were coded and graded by a blinded observer to determine quantity, homogeneity, and fragmentation of fibrillin.
Results:
Observed fibrillin abnormalities in MFS and control patients were limited to the midportion (elastin-associated microfibrils) of the aortic valve, aortic wall, and mitral valve tissues. Fibrillin abnormalities of aortic valve, aortic wall, and mitral valve tissues were seen in all patients with MFS and were most severe in those older than 20 years. Similar fibrillin abnormalities of aortic valve and aortic wall specimens were observed in control patients more than 60 years old.
Conclusions:
Even in the setting of a normal-appearing aortic valve, the current rationale for widespread use of valve-sparing repairs of aortic root aneurysms in patients with MFS and patients older than 60 years should be carefully reexamined in light of these findings.
Insights
Fibrillin abnormalities in aortic and mitral valves are present in Marfan syndrome (MFS) and older adults. These findings challenge valve-sparing aortic root repair in MFS and elderly patients.
Area of Science:
- Cardiovascular Surgery
- Connective Tissue Disorders
- Molecular Biology
Background:
- Marfan syndrome (MFS) involves fibrillin defects, impacting cardiovascular, skeletal, and ocular tissues.
- Bentall procedure is standard for MFS aortic aneurysms, but valve-sparing techniques are gaining interest.
- Prosthetic valve complications drive the search for alternatives to traditional MFS aortic aneurysm repair.
Purpose of the Study:
- To investigate fibrillin content and architecture in aortic and mitral valves of MFS patients.
- To compare fibrillin in MFS patients with controls, including those with isolated valvular disease.
- To assess the implications of fibrillin abnormalities for valve-sparing aortic root repair.
Main Methods:
- Studied 15 patients undergoing valvular heart disease surgery (9 MFS, 6 non-MFS).
- Collected aortic valve, ascending aorta, and mitral valve specimens for fibrillin analysis.
- Utilized indirect immunofluorescence for fibrillin immunostaining and blinded grading of quantity, homogeneity, and fragmentation.
Main Results:
- Fibrillin abnormalities were observed in the midportion of aortic and mitral valve tissues in all MFS patients.
- Abnormalities were more severe in MFS patients over 20 years old.
- Similar, though less severe, fibrillin abnormalities were noted in aortic valve and wall specimens of control patients over 60 years old.
Conclusions:
- Fibrillin abnormalities in aortic and mitral valves are not exclusive to Marfan syndrome.
- The study questions the routine use of valve-sparing aortic root repairs in MFS patients and those over 60.
- Careful reevaluation of valve-sparing repair indications is recommended based on observed fibrillin alterations.