Structural abnormalities in vascular smooth muscle cells in Marfan Syndrome and Bicuspid Aortic Valve Aneurysm

Thoracic aortic aneurysm (TAA) associated with Marfan syndrome (MFS) and bicuspid aortic valve (BAV) is characterized histologically by vascular smooth muscle cell (VSMC) loss, areas of cystic medial necrosis and patchy elastic tissue destruction in the tunica media. In this study we identified the relationship between morphological changes in VSMC and disorganization of aortic wall structure using light microscopy (LM) and transmission electron microscopy (TEM). No TEM study of MFS or BAV VSMC has been previously reported. Aortic tissue was collected from normal aorta (1M; 4F; age 39 ± 14 yr), MFS (5M; 3F; age 35 ± 11 yr) and BAV (6M; 5F; age 57 ± 16 yr). Aortic tissue and cultured VSMC derived from tissue were processed and embedded in resin. Semi thin sections were cut and stained with toluidine blue for LM and viewed at a magnification of 1000x and ultra thin sections were cut for TEM analysis at a magnification of 25000x. Organelles including the mitochondria, endoplasmic reticulum and Golgi apparatus appeared normal in each group. Apart from the presence of cystic medial necrosis reported previously in MFS and BAV aneurysm, LM study revealed generalized severe structural abnormalities of VSMC that were independent of areas of cystic medial necrosis. VSMC contained numerous vacuoles and structural masses occupying most of the cytoplasmic region (normal=10.1±0.1 %; MFS=34.0±0.1%; BAV=29.1±0.1%). Many VSMC were partly disintegrated lying between intact elastic lamellae (normal=1.4±0.1%; MFS=5.3±0.1%; BAV=10.0±0.1%). TEM study showed a loss of interdigitation between VSMC and elastic lamellae. Calcification of VSMC and extracellular matrix components were common findings in BAV. Cultured VSMC showed bulging intracellular masses, tearing of the cytoplasmic membrane, cellular indentations and disintegration. The findings suggest that morphological VSMC changes were present prior to recognizable alterations of elastic lamellae, and that the primary defect in the pathogenesis of TAA arises within the VSMC