However, the role of furin invivo has been complicated by a recent study demonstratingthat an increase in furin might suppress the progression of atherosclerosis.121 Female Apoe–/– mice fed a high-fat diet and with furin overexpression have enhancedmacrophage autophagy, attenuated growth of intra-aortic plaques, andreduced plaque vulnerability.121 In addition,aortic tissues from five patients who underwent the Bentall procedureshowed increased furin levels and autophagic markers in the plaque.121 Whether this controversial observation is aresult of sex difference requires further research. This evidence concerns the gene FURIN and atherosclerosis.