Abstract
Background: Atherosclerosis, which is the principal cause of heart attacks and strokes, is the leading cause of death in the United States. Various biological processes such as apoptosis and autophagy are involved in almost every stage of atherosclerosis, which could lead to plaque instability causing stroke and death. Fatty Acid Binding Protein 4 (FABP4) is an adipokine released by macrophages and is involved in multiple disease conditions including stroke. However, the association of FABP4 with macrophage apoptosis and autophagy in atherosclerosis has not been elucidated. We hypothesize that silencing FABP4 protein could be a novel therapeutic approach to attenuate macrophage apoptosis and autophagy thereby minimizing plaque instability in atherosclerosis. Methods: RAW264 mouse macrophage cells were transfected with siRNA control liposome quantum dots (QD), siFABP4 liposome QD at the concentration of 150 μg/ml total lipids, or TNF-α at 100 ng/ml. Western blot and reverse phase protein array (RPPA) analysis were completed. Results: Inhibiting the translation of FABP4 blocked the apoptotic pathway as evidenced from the increased expression of anti-apoptotic BCL-xL and BCL-2 along with reduced expression of BAX and activated Caspase 3 levels. Beclin-1 and LC3-II levels were also reduced with knocking down FABP4 indicating the attenuation of autophagy. Conclusion: Targeting FABP4 protects against macrophage processes associated with the progression of atherosclerosis.
Highlights
Atherosclerosis is one of the leading causes of death in the world [1] which is characterized by lipid accumulation and inflammation
Mouse macrophage cell line-RAW264 cells when incubated with control and Fatty Acid Binding Protein 4 (FABP4) short-interfering RNA (siRNA)-quantum dots (QD); the siRNA was taken up into the cells (Figure 1(A))
This was supported by the expression of FABP4 protein in control siRNA whereas it is significantly downregulated in treated cells (Figure 1(B))
Summary
Atherosclerosis is one of the leading causes of death in the world [1] which is characterized by lipid accumulation and inflammation. These two processes differentiate atherosclerosis from other chronic inflammatory disorders. Atherosclerosis, which is the principal cause of heart attacks and strokes, is the leading cause of death in the United States Various biological processes such as apoptosis and autophagy are involved in almost every stage of atherosclerosis, which could lead to plaque instability causing stroke and death. We hypothesize that silencing FABP4 protein could be a novel therapeutic approach to attenuate macrophage apoptosis and autophagy thereby minimizing plaque instability in atherosclerosis.
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