, Volume 29, Issue 1, pp 4-11

Atherosklerose und Arteriitis

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Zusammenfassung.

Den meisten kardiovaskulären Erkrankungen liegt ein arteriosklerotischer Umbau des Gefäßsystems zugrunde. In jüngerer Zeit wurden die Bedeutung inflammatorischer Prozesse für die Entwicklung der Arteriosklerose und deren Folgekrankheiten erkannt und die Arteriosklerose als chronische Entzündung identifiziert. Im frühen, makroskopisch nicht identifizierbaren Stadium der Endotheldysfunktion stehen erhöhte Endothelpermeabilität, Expression von Adhäsionsmolekülen sowie Anheftung und Immigration von Leukozyten im Vordergrund. Die Induktion von oxidativem Stress, u. a. durch Stimulation der vaskulären NAD(P)H-Oxidase, scheint dabei eine zentrale Rolle zu spielen. Wiewohl die experimentelle Datenlage zur inflammatorischen Genese der Arteriosklerose schlüssig ist, sind die sich daraus ergebenden therapeutischen Konsequenzen weniger klar. Prospektive Studien mit Antibiotika oder Antioxidanzien fielen bislang eher enttäuschend aus. Allerdings gibt es gute Evidenz dafür, dass ein Teil der Effekte der bei kardiovaskulären Erkrankungen etablierten Medikamente, wie der Statine und der Hemmer des Renin-Angiotensin-Aldosteron-Systems, über eine antiinflammatorische und antioxidative Wirkung zustande kommt. Zur Thematik der Antioxidanzien bleibt festzuhalten, dass neue Studien mit besserem Design und/oder adäquater statistischer Power abgewartet werden müssen.

Abstract.

Cardiovascular disease, the most common cause of death in the Western world, results mainly from atherosclerotic remodeling of the arterial system. Atherosclerosis defines a disease in which the arterial wall becomes thickened and loses elasticity. This is clearly not a static condition. Instead, atherogenesis reflects a continuous development over time, ranging from macroscopically intact arteries to ruptured sclerotic plaques. Different stages at different sites can be present simultaneously within one individual. The pathophysiology of atherogenesis comprises various important steps, including enhanced endothelial permeability, expression of adhesion molecules, monocyte adhesion and immigration, foam cell formation, fatty streaks, smooth muscle cell migration and plaque formation, and, finally, plaque rupture and thrombus formation. In recent years, atherosclerosis is more and more being recognized as a chronic inflammatory process. The hypothesis of a chronic inflammation in atherosclerosis is supported by the following findings: atherosclerosis is associated with enhanced serum levels of inflammation parameters, including in particular C-reactive protein (CRP, Table 1); the atherosclerotic artery produces different hydrolytic enzymes, adhesion molecules, cytokines, and growth factors as seen in chronic inflammation; cells found in early atherosclerotic lesions are typically inflammatory cells (monocytes/ macrophages and T-lymphocytes); and, there is convincing clinical and experimental evidence that formation of reactive oxygen species (ROS) is augmented during this chronic inflammatory process due to an imbalance between synthesis of ROS and neutralizing antioxidative defense mechanisms. Studies in the general population could clearly show that markers of inflammation, in particular CRP, predict the cardiovascular risk. It is the aim of this review to discuss the role of inflammatory processes for the development of atherosclerosis and cardiovascular disease. Pro-inflammatory substances contributing to oxidative stress are listed in Table 2, and particular emphasis is placed on pathophysiologic effects induced by oxidized LDL and angiotensin II. Figure 1 summarizes important reaction steps of oxidative stress reactions, based on formation of superoxide anion (O2 ). Finally, therapeutic options are presented, although it has to be emphasized that treatment with antibiotics proved to be essentially ineffective, and treatment options with antioxidants are not sufficiently evaluated to allow a final statement. Meanwhile, however, there is accumulating evidence that established treatment regimens with statins or renin-angiotensin system inhibitors possess profound anti-inflammatory and antioxidative properties which may support their beneficial effects on cardiovascular disease.