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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
GDF-15 Deficiency Reduces Autophagic Activity in Human Macrophages In Vitro and Decreases p62-Accumulation in
Aline Heduschke1, Kathrin Ackermann1, Beate Wilhelm1
1Institute for Anatomy and Cell Biology, Department of Medical Cell Biology, Philipps-University of Marburg, 35032 Marburg, Germany.
Abstract:
(1) Background: Growth differentiation factor-15 (GDF-15) is associated with cardiovascular diseases and autophagy in human macrophages (MΦ). Thus, we are interested in investigating autophagic mechanisms with special respect to the role of GDF-15. (2) Methods: Recombinant (r)GDF-15 and siRNA GDF-15 were used to investigate the effects of GDF-15 on autophagic and lysosomal activity, as well as autophagosome formation by transmission electron microscopy (TEM) in MΦ. To ascertain the effects of GDF-15-/- on the progression of atherosclerotic lesions, we used GDF-15-/-/ApoE-/- and ApoE-/- mice under a cholesterol-enriched diet (CED). Body weight, body mass index (BMI), blood lipid levels and lumen stenosis in the brachiocephalic trunk (BT) were analyzed. Identification of different cell types and localization of autophagy-relevant proteins in atherosclerotic plaques were performed by immunofluorescence. (3) Results: siGDF-15 reduced and, conversely, rGDF-15 increased the autophagic activity in MΦ, whereas lysosomal activity was unaffected. Autophagic degradation after starvation and rGDF-15 treatment was observed by TEM. GDF-15-/-/ApoE-/- mice, after CED, showed reduced lumen stenosis in the BT, while body weight, BMI and triglycerides were increased compared with ApoE-/- mice. GDF-15-/- decreased p62-accumulation in atherosclerotic lesions, especially in endothelial cells (ECs). (4) Conclusion: GDF-15 seems to be an important factor in the regulation of autophagy, especially in ECs of atherosclerotic lesions, indicating its crucial pathophysiological function during atherosclerosis development.
Insights
Growth differentiation factor-15 (GDF-15) regulates autophagy in macrophages and endothelial cells. Lowering GDF-15 reduced atherosclerosis progression in mice, highlighting its role in cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Cellular Autophagy
- Molecular Mechanisms of Atherosclerosis
Background:
- Growth differentiation factor-15 (GDF-15) is implicated in cardiovascular diseases and macrophage autophagy.
- Understanding the precise role of GDF-15 in autophagic processes is crucial for cardiovascular research.
Purpose of the Study:
- To investigate the impact of GDF-15 on autophagic and lysosomal activity in macrophages.
- To evaluate the role of GDF-15 in the development of atherosclerosis using a mouse model.
Main Methods:
- Utilized recombinant GDF-15 and siRNA GDF-15 to assess autophagic activity in macrophages via transmission electron microscopy (TEM).
- Employed GDF-15 knockout (GDF-15-/-) and ApoE knockout (ApoE-/-) mice on a cholesterol-enriched diet to study atherosclerotic lesion progression.
- Analyzed lumen stenosis, body weight, BMI, lipid profiles, and protein localization (p62) in atherosclerotic plaques using immunofluorescence.
Main Results:
- Recombinant GDF-15 enhanced autophagic activity in macrophages, while siRNA GDF-15 reduced it; lysosomal activity remained unchanged.
- GDF-15-/-/ApoE-/- mice exhibited decreased brachiocephalic trunk lumen stenosis but increased body weight, BMI, and triglycerides compared to ApoE-/- mice.
- GDF-15 deficiency led to reduced p62 accumulation in atherosclerotic lesions, particularly within endothelial cells.
Conclusions:
- GDF-15 plays a significant role in regulating autophagy, especially in endothelial cells within atherosclerotic lesions.
- GDF-15 appears to be a key pathophysiological factor in the development and progression of atherosclerosis.
