Der interzelluläre Transport Lipid-geladener Lysosomen aus Makrophagen in glatte Gefäßmuskelzellen führt zur phänotypischen Veränderung der Gefäßmuskelzellen in einen schaumzellartigen Phänotyp

Sönke Weinert

AutorIn

Sönke Weinert

Titel

Der interzelluläre Transport Lipid-geladener Lysosomen aus Makrophagen in glatte Gefäßmuskelzellen führt zur phänotypischen Veränderung der Gefäßmuskelzellen in einen schaumzellartigen Phänotyp

Zitierfähige Url:

https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa-150397

Datum der Einreichung

27.11.2013

Datum der Verteidigung

27.06.2014

Abstract (EN)

AIMS: Macrophages (MPs) and vascular smooth muscle cells (VSMCs) closely interact within the growing atherosclerotic plaque. An in vitro co-culture model was established to study how MPs modulate VSMC behaviour. METHODS AND RESULTS: MPs were exposed to fluorescence-labelled-acetylated LDL (FL-acLDL) prior to co-culture with VSMCs. Fluorescence microscopy visualized first transport of FL-acLDL within 6 h after co-culture implementation. When MPs had been fed with FL-acLDL in complex with fluorescence-labelled cholesterol (FL-Chol), these complexes were also transferred during co-culture and resulted in cholesterol positive lipid droplet formation in VSMCs. When infected with a virus coding for a fusion protein of Rab5a and fluorescent protein reporter (FP) to mark early endosomes, no co-localization between Rab5a-FP and the transported FL-acLDL within VSMCs was detected implying a mechanism independent of phagocytosis. Next, expression of lysosome-associated membrane glycoprotein 1 (LAMP1)-FP, marking all lysosomes in VSMCs, revealed that the FL-acLDL was located in non-acidic lysosomes. MPs infected with virus encoding for LAMP1-FP prior to co-culture demonstrated that intact fluorescence-marked lysosomes were transported into the VSMC, instead. Xenogenic cell composition (rat VSMC, human MP) and subsequent quantitative RT-PCR with rat-specific primers rendered induction of genes typical for MPs and down-regulation of the cholesterol sensitive HMG-CoA reductase. CONCLUSION: Our results demonstrate that acLDL/cholesterol-loaded lysosomes are transported from MPs into VSMCs in vitro. Lysosomal transfer results in a phenotypic alteration of the VSMC towards a foam cell-like cell. This way VSMCs may lose their plaque stabilizing properties and rather contribute to plaque destabilization and rupture.

Freie Schlagwörter (DE)

Gefäßmuskelzellen, Makrophagen, Low Density Lipoprotein, LDL, Cholesterol

Freie Schlagwörter (EN)

Smooth muscle cells, Macrophages, Low-density lipoprotein (LDL), Cholesterol

Klassifikation (DDC)

540

Klassifikation (RVK)

WD 5400

GutachterIn