IMPORTANCE OF CELLULAR-DIFFERENTIATION AN D CONCOMITANT ALTERATIONS OF THE EXTRACELLULAR-MATRIX IN THE PATHOGENESIS OF THE ARTERIOSCLEROTICINTIMA FIBROSIS

The analysis of cellular and extracellular alterations in the composit ion of the vascular wall represents the ground basis for the understan ding of the pathogenesis of arteriosclerotic intima lesions. We immuno histochemically analyzed the distribution of important cellular and ex tracellular markers in 117 arteriosclerotic vessel biopsies obtained b y directional atherectomy (acc. to Simpson) of iliacal, femoral and co ronary arteries. These markers comprised the cellular filaments viment in (connective tissue cells), alpha-smooth muscle (SMC) actin (SMCs an d myofibroblasts) and desmin (SMCs), as well as the interstitial matri x markers collagen I, III, V and VI and the basement membrane componen ts collagen IV, laminin, heparan sulfate proteoglycan and fibronectin. The distinction between poorly and highly cellular intima areas coinc ided with specific changes particularly in the extracellular matrix co mposition. While highly cellular intimal tissue demonstrated a loose f ibrosis mainly composed of collagens III, V and VI, the poorly cellula r fibrotic intima contained predominantly collagen I. The respective c ells showed a cytoplasmic expression of vimentin and alpha-SMC actin, but not of the muscle specific filament desmin. This constellation of extensive matrix production along with SMC-muscular actin expression i n the highly cellular areas points to a >>myofibroblastic phenotype<< of these cells. This is confirmed by the presence of a pericellular ba sement membrane. The quantitative basement membrane composition in poo rly cellular areas additionally provides evidence for a tendency of sm ooth muscle >>redifferentiation<< of certain cells in this late stage of intima fibrosis. Our observations thus demonstrate that specific ch anges in the cellular differentiation and concomitant alterations of t he extracellular matrix are highly significant for the explanation of pathogenetic mechanisms of arteriosclerotic intima fibrosis.