Inflammation and coagulation in atherosclerosis

 

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Summary

Cardiovascular diseases remain to be the leading cause of death in Western societies. Despite major findings in vascular biology that lead to a better understanding of the pathomechanisms involved in atherosclerosis, treatment of the disease has only changed slightly within the last years. A big body of evidence suggests that atherosclerosis is a chronic inflammatory disease of the vessel wall. Accumulation and peroxidation of LDL-particles within the vessel wall trigger a strong inflammatory response, causing macrophage and T-cell accumulation within the vessel wall. Additionally, B-cells and specific antibodies against LDL-particles, as well as the complement system are implicated in atherogenesis. Besides data from clinical trials and autopsy studies it was the implementation of mouse models of atherosclerosis and the emerging field of direct genmodification that lead to a thorough description of the pathophysiological mechanisms involved in the disease and created overwhelming evidence for a participation of the immune system. Recently, the cross-talk between coagulation and inflammation in atherogenesis has gained attention. Serious limitations and disparities in the pathophysiology of atherosclerosis in mice and men complicated the translation of experimental data into clinical practice. Despite these limitations, new anti-inflammatory medical therapies in cardiovascular disease are currently being tested in clinical trials.

Zusammenfassung

Kardiovaskuläre Erkrankungen sind noch immer die häufigste Todesursache in der westlichen Welt. Trotz neuer Erkenntnisse aus der vaskulären Biologie, die zu einem besseren Verständnis der Pathomechanismen in der Atherosklerose geführt haben, hat sich die Therapie der Erkrankung in den vergangenen Jahren nicht wesentlich geändert. Die Atherosklerose wird heute als chronisch inflammatorische Erkrankung der Gefäßwand betrachtet. Zelluläre und humorale Bestandteile des Immunsystems, z. B. Makrophagen und T-Zellen, aber auch B-Zellen und spezifische Antikörper gegen akkumulierende LDL-Partikel in der Gefäßwand spielen eine wichtige Rolle in der Pathophysiologie dieser Erkrankung. Neben Daten aus klinischen Beobachtungswie auch aus Autopsiestudien, war vor allem die Möglichkeit gezielter Genmodifikation und die Etablierung geeigneter Tiermodelle ausschlaggebend für die detaillierte Beschreibung entzündlicher Prozesse in der Atherogenese.

Das Zusammenspiel zwischen Koagulation und Inflammation in der Atherogenese hat in letzter Zeit wieder mehr Aufmerksamkeit erlangt. Limitationen des Mausmodells und Unterschiede in der Pathophysiologie der Erkrankung in Tier und Mensch erschwerten bisher die Umsetzung der experimentellen Daten im klinischen Alltag. Trotz dieser Limitationen befinden sich heute mehrere gezielt anti-inflammatorische medikamentöse Therapien in klinischer Prüfung.

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