Lei Gao
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Lei Gao has a total of 39 co-authors. Here are the top co-authors by number of shared publications:
- Allison M. Quick
The Ohio State University Comprehensive Cancer Center 3 Department of Radiation Oncology James Cancer Hospital and Solove Research Institute, Columbus, Ohio
1 shared publication - Anthony W. Ashton
Division of Perinatal Research Kolling Institute of Medical Research Sydney New South Wales Australia
1 shared publication - Atsumi Tsuji-Hosokawa
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Setagaya-ku, Japan
1 shared publication - Ayako Makino
University of Florida
1 shared publication - Bradley Monk
Florida Cancer Specialists and Research Institute, West Palm Beach, FL, USA
1 shared publication - Brian T. Scott
Department of Medicine, University of California, San Diego, La Jolla, California
1 shared publication
Latest Publications
- Open Access
- 8 November 2021
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 6 (21)
HuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes
Patients with diabetes with coronary microvascular disease (CMD) exhibit higher cardiac mortality than patients without CMD. However, the molecular mechanism by which diabetes promotes CMD is poorly understood. RNA-binding protein human antigen R (HuR) is a key regulator of mRNA stability and translation; therefore, we investigated the role of HuR in the development of CMD in mice with type 2 diabetes. Diabetic mice exhibited decreases in coronary flow velocity reserve (CFVR; a determinant of coronary microvascular function) and capillary density in the left ventricle. HuR levels in cardiac endothelial cells (CECs) were significantly lower in diabetic mice and patients with diabetes than the controls. Endothelial-specific HuR-KO mice also displayed significant reductions in CFVR and capillary density. By examining mRNA levels of 92 genes associated with endothelial function, we found that HuR , Cx40 , and Nox4 levels were decreased in CECs from diabetic and HuR -KO mice compared with control mice. Cx40 expression and HuR binding to Cx40 mRNA were downregulated in CECs from diabetic mice. Cx40 -KO mice exhibited decreased CFVR and capillary density, whereas endothelium-specific Cx40 overexpression increased capillary density and improved CFVR in diabetic mice. These data suggest that decreased HuR contributes to the development of CMD in diabetes through downregulation of gap junction protein Cx40 in CECs.
- 8 November 2021
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 6 (21)
Open AccessHuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes
Patients with diabetes with coronary microvascular disease (CMD) exhibit higher cardiac mortality than patients without CMD. However, the molecular mechanism by which diabetes promotes CMD is poorly understood. RNA-binding protein human antigen R (HuR) is a key regulator of mRNA stability and translation; therefore, we investigated the role of HuR in the development of CMD in mice with type 2 diabetes. Diabetic mice exhibited decreases in coronary flow velocity reserve (CFVR; a determinant of coronary microvascular function) and capillary density in the left ventricle. HuR levels in cardiac endothelial cells (CECs) were significantly lower in diabetic mice and patients with diabetes than the controls. Endothelial-specific HuR-KO mice also displayed significant reductions in CFVR and capillary density. By examining mRNA levels of 92 genes associated with endothelial function, we found that HuR , Cx40 , and Nox4 levels were decreased in CECs from diabetic and HuR -KO mice compared with control mice. Cx40 expression and HuR binding to Cx40 mRNA were downregulated in CECs from diabetic mice. Cx40 -KO mice exhibited decreased CFVR and capillary density, whereas endothelium-specific Cx40 overexpression increased capillary density and improved CFVR in diabetic mice. These data suggest that decreased HuR contributes to the development of CMD in diabetes through downregulation of gap junction protein Cx40 in CECs.