title: High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker.
abstract: Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: He Yun
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Park
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Woong Bi
authors.initials: WB
authors.lastname: Jang
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Seung Taek
authors.initials: ST
authors.lastname: Ji
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Seok Yun
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Da Yeon
authors.initials: da Y
authors.lastname: Kim
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Songhwa
authors.initials: S
authors.lastname: Kang
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Yeon Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Jisoo
authors.initials: J
authors.lastname: Yun
authors.affiliation: Research Institute of Convergence Biomedical Science and Technology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Laboratory of Cardiovascular Disease, Seoul St. Mary's Hospital, School of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Sang Hong
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kwon
keywords: Cardiac progenitor cell; Diabetic cardiomyopathy; Fasentin; Hyperglycemia; Mitochondrial dynamics