The Role of Endoplasmic Reticulum Stress-Glycogen Synthase Kinase-3 Signaling in Atherogenesis.

Cardiovascular disease (CVD) is the number one cause of global mortality and atherosclerosis is the underlying cause of most CVD. However, the molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are not well understood. The development of new efficient therapies to directly block or slow disease progression will require a better understanding of these mechanisms. Accumulating evidence supports a role for endoplasmic reticulum (ER) stress in all stages of the developing atherosclerotic lesion however, it was not clear how ER stress may contribute to disease progression. Recent findings have shown that ER stress signaling through glycogen synthase kinase (GSK)-3α may significantly contribute to macrophage lipid accumulation, inflammatory cytokine production and M1macrophage polarization. In this review we summarize our knowledge of the potential role of ER stress-GSK3 signaling in the development and progression of atherosclerosis as well as the possible therapeutic implications of this pathway.