Cardiac amyloid in patients with familial amyloid polyneuropathy consists of abundant wild-type transthyretin

Patients with familial amyloid polyneuropathy (FAP) are now cured by liver transplantation, but cardiac amyloidosis would further progress even after liver transplantation in some patients. To clarify the pathological mechani sm of the progress of cardiac amyloidosis in FAP, we investigated cardiac t issues obtained from 6 FAP patients with 3 different types of TTR mutations . One of them had undergone liver transplantation and one year later died o f cardiac amyloidosis. We determined clinical severity of cardiac involveme nt of those patients and characterized amyloid fibril proteins depositing i n their cardiac muscles by immunohistochemistry, mass spectrometry and isoe lectric focusing. All the patients had cardiac dysfunction and increased ca rdiac weight. Diffuse deposition of TTR-related amyloid was seen in their m yocardium on microscopic examination. Amyloid fibrils of the heart were com posed of wild-type TTR as well as variant TTR at a ratio of about 1:1 in 5 patients without liver transplantation. In the patient with a transplanted liver, about 80% of the cardiac amyloid consisted of wild-type TTR. Wild-ty pe TTR contributes greatly to the development of amyloid deposition in the heart of FAP patients regardless of the types of TTR mutations. (C) 2000 Ac ademic Press.