Abstract
BackgroundThe cytokine growth differentiation factor-15 (GDF-15), a member of the TGF beta superfamily, has recently been discovered to play an important role in cardiovascular diseases. It is mostly expressed in macrophages of atherosclerotic lesions, but its impact on advanced atherosclerosis is still unknown. This study was performed to evaluate the effects of GDF-15 in an established mouse model of advanced atherosclerosis.MethodsThirty-eight LDL receptor deficient mice received a lethal body radiation. Half of the group was transplanted with bone marrow of GDF-15 deficient mice. Nineteen mice were transplanted with bone marrow from wild-type controls. After 24 weeks on an atherogenic diet, animals were euthanized and sections of the aortic sinus were prepared. Lesion size and lesion composition, as well as macrophage content,were evaluated.ResultsWhile demonstrating no difference in lesion size, LDL-receptor knockout mice transplanted with bone marrow from GDF-15 deficient mice showed enhanced macrophage accumulation and features of atherosclerotic plaque destabilization, such as thinning of fibrous caps. Immunostaining against intercellular adhesion molecule-1 further revealed an increased expression in mice receiving GDF-15-deficient bone marrow.ConclusionsThis is the first study that demonstrates a protective role of GDF-15 in advanced atherosclerosis and macrophage accumulation, possibly due to the reduced expression of adhesion molecules.
Highlights
The cytokine growth differentiation factor-15 (GDF-15), a member of the TGF beta superfamily, has recently been discovered to play an important role in cardiovascular diseases
Most experimental studies have demonstrated the anti-atherogenic properties of transforming growth factor-β (TGF-β) [14,15]; these have not been defined for the different members of the TGF-β superfamily [2,16]
It is not known how GDF-15 acts in the advanced stages of atherosclerosis that we often find in human disease
Summary
The cytokine growth differentiation factor-15 (GDF-15), a member of the TGF beta superfamily, has recently been discovered to play an important role in cardiovascular diseases. It is mostly expressed in macrophages of atherosclerotic lesions, but its impact on advanced atherosclerosis is still unknown. A study by de Jager et al.demonstrated an anti-atherosclerotic effect of GDF15 deficiency in low-density lipoprotein (LDL)r−/− mice 4 and 12 weeks after initiation of a hyperlipidemic diet [17] It is not known how GDF-15 acts in the advanced stages of atherosclerosis that we often find in human disease. We tested whether GDF-15 alters lesion size and lesion composition in an advanced stage of atherosclerosis
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