Objectives: Desmin mutations have been reported among others as a cause for dilated and restrictive cardiomyopathies. Amyloid formation has been speculated to be involved in the pathogenesis of this type of cardiomyopathy. Recently, we reported a desmin mutation, transmitted over several generations. This L345P missense mutation has a dominant-negative effect on filament formation, causing myopathy and cardiomyopathy. Transgenic animals with mutated desmin gene (DM) were constructed and analysed.
Material and methods: DM and wild-type mice 70 weeks old were analysed. Myocardial cryostat sections were stained with hematoxilin-eosin, Van-Gieson and Congo Red.
Results: DM mice showed cardiac hypertrophy and decreased LV dimensions. Cardiac sections showed an increase of stromal cell number, due to lymphocyte and fibroblast-like cell infiltration, and interstitial fibrosis. The most prominent feature of DM mice myocardium was focal amorphic protein depositions in arterial adventitia and perivascular space and between muscle fibers. These protein depositions were also observed intracellular in subsarcolemmal spaces and were slightly stained with eosin and fuscin. The amyloid nature of these depositions was confirmed by positive Congo-Red staining in light microscopy and dark field. Degree of cardiomyocyte disarray varied from mild to moderate, being more prominent in areas of fiber disruption and protein depositions. None of these changes were observed in control mice.
Conclusions: The L345P desmin mutation causes focal amyloid protein deposition in heart muscle, accompanied by an increase in stromal cell numbers and formation of granulomas. These data further support that amyloidosis can be responsible for the development of desmin-related cardiomyopathy.