G. Schettler – författare

Even though numerous questions with regard to the pathogenesis of athero­ sclerosis have not yet been answered, the accumulated evidence indicates significant regression of lesions in experimental animals. This is discussed extensively in this monograph, as are the mechanisms involved in regression of lesions. Whether human atherosclerosis has the potential for regression appears to be the most important, but at the same time the most difficult question to answer. Contrary to experimental atherosclerosis in animals, which can be produced and which can regress within a few months, human lesions in general develop slowly over many years. Therefore, measures aimed at modifying this process may also require many years to be successful. In addition, repeated direct examination of lesions in the human is usually not possible. Nevertheless, recent reports in patients with hyperlipoproteinemias indicate that pronounced and maintained control of hyperlipidemias may lead, even within months, to regression as evidenced by angiography or sophisticated measurements of peripheral circulation. The monograph is divided into two sections. The first will deal with of lipid deposition in the arterial wall, whether "atherogenesis": mechanisms or not there is evidence of monoclonal origin of human atherosclerosis plaques, cell culture and factors that stimulate smooth muscle proliferation, and animal models of atherogenesis. This section is concluded with a discussion of dietary factors other than lipids in atherogenesis.

Probleme des Lipidstoffwechsels beruhren zahlreiche Bereiche der arztlichen Tatigkeit in Praxis und Klinik. Hyperlipidamien sind die haufigsten Stoffwechselstorungen geworden ~ als Risikofaktor arte- riosklerotischer Erkrankungen sind sie mitverantwortlich fUr die haufigste Todesursache, den Herzinfarkt. Der vorliegende Handbuchband spiegelt die Fortschritte unserer Kenntnis uber den normalen und gestorten Fettstoffwechsel wider. 38 internationale Autoren behandeln die physiologischen und patho- physiologischen Grundlagen der Lipide und Lipoproteine, primare und sekundare Hyperlipoproteinamien, Hypolipoproteinamien und Lipidosen. Die Darstellung der Hyperlipoproteinamien berucksichtigt die Fortschritte der Lipoproteinforschung und die Einteilung, wie sie von Fredrickson und Mitarbeitern vorgeschlagen und von einem AusschuB der WHO als Vorschlag einer gemeinsamen Sprache auf diesem Gebiet unterstutzt wurde.Dabei sind sich Autoren und Herausgeber daruber im klaren, daB eine derartige Darstellung zum Teil noch vorwiegend deskriptiv ist und ein und dasselbe Lipo- proteinmuster sowohl bei verschiedenen genetischen Storungen des Lipidstoffwechsels als auch bei sekundaren Hyperlipoproteinamien beobachtet werden kann. Das Einteilungssystem muB daher so lange flexibel bleiben, bis eine Klassifizierung, die auf der Pathogenese dieser klinisch wichtigen Stoffwechselstorung beruht, moglich ist. Die jiingsten Fortschritte der Forschung auf diesem Gebiet haben bereits zu konkreten Ergebnissen gefiihrt und lassen neue Ansatze erkennen. Ein Vergleich der vorliegenden Darstellung der verschiedenen Lipidosen mit den entsprechenden Kapiteln im Handbuch von 1955 zeigt, daB hier die Aufklarung der Atiologie weitgehend abgeschlos- sen ist und verschiedene Storungen des enzymatischen Abbaus dieser komplexen Lipide bereits in utero nachgewiesen werden konnen.

Even though numerous questions with regard to the pathogenesis of athero­ sclerosis have not yet been answered, the accumulated evidence indicates significant regression of lesions in experimental animals. This is discussed extensively in this monograph, as are the mechanisms involved in regression of lesions. Whether human atherosclerosis has the potential for regression appears to be the most important, but at the same time the most difficult question to answer. Contrary to experimental atherosclerosis in animals, which can be produced and which can regress within a few months, human lesions in general develop slowly over many years. Therefore, measures aimed at modifying this process may also require many years to be successful. In addition, repeated direct examination of lesions in the human is usually not possible. Nevertheless, recent reports in patients with hyperlipoproteinemias indicate that pronounced and maintained control of hyperlipidemias may lead, even within months, to regression as evidenced by angiography or sophisticated measurements of peripheral circulation. The monograph is divided into two sections. The first will deal with of lipid deposition in the arterial wall, whether "atherogenesis": mechanisms or not there is evidence of monoclonal origin of human atherosclerosis plaques, cell culture and factors that stimulate smooth muscle proliferation, and animal models of atherogenesis. This section is concluded with a discussion of dietary factors other than lipids in atherogenesis.

Advances which have been made in the field of lipid chemistry and bio- chemistry during the last ten years mainly are the results of progress in metho- dology. The introduction of isotopic and chromatographic techniques has not only enriched our knowledge of normal lipid metabolism but has also greatly enhanced the understanding of the various lipidoses. This is well illustrated by a comparison of the contents of the present monograph with those of my 1955 review in Handbuch der Inneren Medizin (Springer). In addition to better information about the classic lipid thesaurismoses Nie- mann-Pick disease, Gaucher's disease and Tay-Sachs disease, the number of hereditary lipid storage diseases has increased considerably through the recogni- tion of new syndromes such as metachromatic leukodystrophy, Fabry's disease, Refsum's disease (heredopathia atactica polyneuritiformis), a-p-lipoproteinemia, and Tangier disease. Conversely, disorders such as Hand-Scholler-Christian disease which has been considered a lipidosis up to 1958 (THANNHAUSER) must now be differentiated from the hereditary disturbances of lipid metabolism.Essential hyperlipemia which at one time seemed to be a well defined entity has now been recognized to consist of a number of subgroups, whose pathogeneses appear to be quite different, and whose classification is by no means definite. Similar problems exist for "essential hypercholesterolemia". Since the knowledge of today is the key for the solutions of tomorrow, we are fortunate that the chapters on lipidoses are supplemented by a comprehensive account of lipid chemistry and biochemistry which has been coordinated by W. STOFFEL.

The presence of monotypism in thick atherosclerotic lesions of black females with G-6-PD mosaicism first reported by the Benditts (1973) has been confirmed in two other laboratories. However, we believe that it is premature to conclude that the finding of monotypism necessarily indicates monoclonal origin of athero­ sclerotic lesions. We have suggested two alternative explanations for the obser­ vation of monotypism which we believe must be shown to be invalid before accept­ ing monoclonal origin as the only plausible way to account for the observed G-6-PD monotypism. One of these two alternatives relates to clonal heterogeneity of cell growth potential, i. e. , during the course of progressive growth of a le­ sion, progeny of one cell may overgrow all others in a portion of the lesion. The other alternative is that one of the G-6-PD alleles may be linked to genes that afford a preferential survival characteristic in the abnormal environment present in atheroscerotic lesions. Thus, cells with one allele may be able to grow better than cells with the other allele, and this characteristic may be unrelated to "A-ness" or "B-ness". We have studied initiation of lesions in He diet-fed swine and demonstrated that all active lesions that were studied were of multiple cell origin (not monoclo­ nal). We have studied cell growth patterns in developing atherosclerotic lesions in He diet-fed swine and found evidence consistent with clonal heterogeneity in growth potential of lesion cells.