Experimentelle Charakterisierung verschiedenartiger Arteriosklerose-Typen als Grundlage einer rationalen Therapie Schlussbericht

In long-term experiments (6-24 months) on rats and rabbits, experimental atheromatoses and arterioscleroses were produced under the influence of various risk factors to further elucidate the atherogenic roles of calcium (Ca) and cholesterol. On the basis of microchemical analyses, incorporation of labelled markers, microscopic studies and therapeutic responsiveness to Ca antagonists and HMG CoA reductase inhibitor (lovastatin), three types could be characterized: (1) Ca-type, i.e Ca overload of arterial walls following vitamin D_3 intoxication or alloxan diabetes in rats: Necrotization of Ca-overloaded media cells, calcification of elastic fibres, secondary intima plaques without any cholesterol incorporation. (2) Cholesterol atheromata as unspecific manifestations of the generalized lipid storage disease of cholesterol-fed rats and rabbits: Intima plaques with foam cells and extracellular cholesterol deposits due to excessive increase in serum cholesterol. (3) Mixed types with Ca and cholesterol accumulations in arteries of SHR (normal serum lipids) and NaCl-fed Dahl-S-rats (hypercholesterolemia) with massive cell proliferation, matrix production, and thrombotic complications. The transfer of the present data to human pathomorphology and therapy remains to be further clarified. However, two principal experimental results encourage to a more differentiated therapeutic strategy - particularly in the prevention of Ca-dominated types of conventional human arteriosclerosis: Lowering of high serum cholesterol cannot definitely prevent cholesterol accumulation into arterial walls, altered by risk factors - particularly hypertension. The antiarteriosclerotic potential of Ca antagonists, demonstrated in various animal models of experimental arteriosclerosis and atheromatosis, covers the prevention of primarily Ca-induced alterations of the arterial walls even in the presence of elevated serum cholesterol levels. (orig./HK)SIGLEAvailable from TIB Hannover: F97B760 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman