Zusammenfassung
Zwischen Veränderungen des High-density-lipoprotein(HDL)-Stoffwechsels und der Atherosklerose besteht eine kausale Beziehung. Um diese Zusammenhänge therapeutisch zu nutzen, sind Kenntnisse über die grundlegenden Prozesse des HDL-Stoffwechsels unumgänglich. Verschiedene Proteine sind entweder als Strukturproteine der Lipoproteine (Apo A-I, Apo A-II, Apo E), als Enzyme oder Transportproteine (z. B. Lecithin-Cholesterin-Acyltransferase [LCAT] oder Cholesterinestertransferprotein [CETP]) oder als zelluläre Transportsysteme (ABCA1, ABCG1, SR-B1) in den HDL-Stoffwechsel involviert. Diese Proteine sind notwendig um den Cholesterinefflux sicherzustellen, aber auch um die antiinflammatorischen, -oxidativen und -thrombotischen Eigenschaften von HDL zu vermitteln. Die Komplexität des HDL-Stoffwechsels macht es schwierig vorherzusagen, ob Interventionen im HDL-Bereich proatherogen, antiatherogen oder neutral sind. Die epidemiologischen wie auch genetischen Daten sprechen aber dafür, dass sich Modulationen am HDL-System letztendlich auch in einer veränderten Atheroskleroserate widerspiegeln. Somit bieten HDL-modifizierende Interventionen einen interessanten Ansatz, das unter Statintherapie weiter bestehende residuale Risiko zu vermindern.
Abstract
Changes in high-density lipoprotein (HDL) metabolism are causally linked to atherosclerosis. Knowledge about HDL metabolism is necessary to use this relationship as a therapeutic approach to address atherosclerosis. Different proteins are involved in HDL metabolism and include structural proteins, such as apolipoprotein A1 (apoA1), apoA2 and apoE, enzymes or transport proteins, such as lecithin-cholesterol acyltransferase (LCAT) or cholesteryl ester transfer protein (CETP) and cellular transporters, such as ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1) and scavenger receptor B1 (SR-B1). These components are necessary to warrant cholesterol efflux and also for the anti-inflammatory, antioxidative and antithrombotic properties of HDL. Because of the complexity of HDL metabolism it is difficult to predict whether interventions affecting HDL levels or function will be proatherogenic, antiatherogenic or neutral. However, the epidemiological as well as the genetic data indicate that modulations of the HDL system will influence atherosclerosis. Therefore, HDL modifying interventions are an interesting approach to address residual risks associated with statin therapy.
Abbreviations
- ABCA1:
-
„ATP-binding cassette transporter A1“
- ABCG1:
-
„ATP-binding cassette transporter G1“
- Apo:
-
Apolipoprotein
- CETP:
-
Cholesterinestertransferprotein
- HDL:
-
„High density lipoprotein“
- HL:
-
Hepatische Lipase
- IDL:
-
„Intermediate density lipoprotein“
- LDL:
-
„Low density lipoprotein“
- LCAT:
-
Lecithin-Cholesterin-Acyltransferase
- PLTP:
-
Phospholipidtransferprotein
- SR-B1:
-
„Scavenger receptor B1“
- TG:
-
Triglyzeride
- VLDL:
-
„Very low density lipoprotein“
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Interessenkonflikt
Der korrespondierende Autor weist auf folgende Beziehungen hin: Vortragshonorare, Honorare für Advisory Board Tätigkeit, Honorare für DMC-Tätigkeit und/oder Forschungsunterstützung von folgenden Unternehmen: Abbott, Astra-Zeneca, Berlin-Chemie, BMS, Fresenius, Genzyme, Kaneka, Kowa, MSD, Novartis, Roche.
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Parhofer, K. Cholesterinrücktransport und HDL-Funktion. Kardiologe 6, 329–336 (2012). https://doi.org/10.1007/s12181-012-0438-3
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DOI: https://doi.org/10.1007/s12181-012-0438-3
Schlüsselwörter
- Cholesterinefflux
- Cholesterinrücktransport
- Apolipoprotein A
- Cholesterinestertransferprotein(CETP)-Inhibition
- Cholesterinestertransferprotein(CETP)-Modulation