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Published on: June 2, 2019
Inhibition of bone morphogenic protein 4 restores endothelial function in db/db diabetic mice
Yang Zhang1, Jian Liu, Xiao Yu Tian
1From the Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences (Y.Z., L.W., J.L., W.S.C., C.W.L., X.Y., Y.H.), School of Biomedical Sciences (J.L., Y.C., X.Y., Y.H.), School of Life Sciences (K.M.K.), Chinese University of Hong Kong, Hong Kong SAR, China; Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX (X.Y.T., W.T.W.); and Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China (N.W.).
Inhibiting bone morphogenic protein 4 (BMP4) signaling improved blood vessel function in diabetic mice. This approach reduced oxidative stress, offering a potential therapy for diabetic vascular dysfunction.
Area of Science:
- Endocrinology and Metabolism
- Vascular Biology
- Molecular Medicine
Background:
- Bone morphogenic protein 4 (BMP4) is implicated in endothelial dysfunction associated with hypertension.
- Diabetic complications often involve impaired vascular function.
Purpose of the Study:
- To investigate if inhibiting BMP4 signaling can enhance endothelial function in a mouse model of diabetes (db/db mice).
Main Methods:
- Male db/db mice were treated with noggin or adenovirus carrying BMP4-short hairpin RNA.
- Vasoreactivity was assessed using wire and pressure myography.
- Reactive oxygen species (ROS) production was measured using various assays.
- Activin receptor-like kinase 3 (ALK3) was silenced using lentivirus.
Main Results:
- Both noggin and BMP4 inhibition improved endothelium-dependent relaxations and flow-mediated dilatation.
- BMP4 inhibition reduced oxidative stress in aortic tissues and endothelial cells.
- Silencing ALK3 also enhanced endothelial function and decreased ROS levels.
- Noggin treatment decreased BMP4 upregulation in high-glucose conditions and in mouse aortae.
Conclusions:
- Inhibition of the BMP4/ALK3/ROS signaling pathway ameliorates endothelial dysfunction in diabetic mice.
- This strategy limits endothelial oxidative stress, suggesting BMP4 inhibition as a therapeutic target for diabetic vascular complications.
