Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease

T Minamino, I Komuro, M Kitakaze - Circulation research, 2010 - Am Heart Assoc
T Minamino, I Komuro, M Kitakaze
Circulation research, 2010Am Heart Assoc
Cardiovascular disease constitutes a major and increasing health burden in developed
countries. Although treatments have progressed, the development of novel treatments for
patients with cardiovascular diseases remains a major research goal. The endoplasmic
reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and
lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in
calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins …
Cardiovascular disease constitutes a major and increasing health burden in developed countries. Although treatments have progressed, the development of novel treatments for patients with cardiovascular diseases remains a major research goal. The endoplasmic reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins lead to the accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers the unfolded protein response (UPR) to maintain ER homeostasis. The UPR involves a group of signal transduction pathways that ameliorate the accumulation of unfolded protein by increasing ER-resident chaperones, inhibiting protein translation and accelerating the degradation of unfolded proteins. The UPR is initially an adaptive response but, if unresolved, can lead to apoptotic cell death. Thus, the ER is now recognized as an important organelle in deciding cell life and death. There is compelling evidence that the adaptive and proapoptotic pathways of UPR play fundamental roles in the development and progression of cardiovascular diseases, including heart failure, ischemic heart diseases, and atherosclerosis. Thus, therapeutic interventions that target molecules of the UPR component and reduce ER stress will be promising strategies to treat cardiovascular diseases. In this review, we summarize the recent progress in understanding UPR signaling in cardiovascular disease and its related therapeutic potential. Future studies may clarify the most promising molecules to be investigated as targets for cardiovascular diseases.
Am Heart Assoc