Novel Ideas of Gene Therapy for Atherosclerosis: Modulation of Cellular Signal Transduction of TGF-β Family

Atherosclerosis is a disease characterized by accumulation of lipids and fibrous elements in the innermost layer of the arterial wall. An asymptomatic atherosclerotic plaque is characterized by a lipid core, composed of modified lipids, macrophages and T cells, which were separated from the lumen vessel by a thick fibrous cap, composed of vascular smooth muscle cell-secreted solid collagen matrix. Recently, it has been reported that expressions of TGF-β family were up regulated in human atherosclerotic plaques. In addition TGF-β family seems to plays pivotal roles for the development of atherosclerosis: TGF-β and activin A were suggested to play protective roles against the development of atherosclerotic plaques. On the other hand bone morphogenetic protein seems to play pivotal roles for the calcification of the atherosclerotic plaques. Therefore, it is debatable whether gene therapy modulating cellular signal transductions of TGF-β family is a useful tool for the inhibition of progression of atherosclerotic disease. In this review, our discussion is focused on the possibilities of gene therapies for atherosclerosis either by enhancement or suppression of cellular signaling of TGF-β family in target cells, in atherosclerotic plaques.