Back to Search
Start Over
High-Density Lipoproteins Rescue Diabetes-Impaired Angiogenesis via Scavenger Receptor Class B Type I
- Source :
- Diabetes. 65:3091-3103
- Publication Year :
- 2016
- Publisher :
- American Diabetes Association, 2016.
-
Abstract
- Disordered neovascularization and impaired wound healing are important contributors to diabetic vascular complications. We recently showed that high-density lipoproteins (HDLs) enhance ischemia-mediated neovascularization, and mounting evidence suggests HDL have antidiabetic properties. We therefore hypothesized that HDL rescue diabetes-impaired neovascularization. Streptozotocin-induced diabetic mice had reduced blood flow recovery and neovessel formation in a hindlimb ischemia model compared with nondiabetic mice. Reconstituted HDL (rHDL) infusions in diabetic mice restored blood flow recovery and capillary density to nondiabetic levels. Topical rHDL application rescued diabetes-impaired wound closure, wound angiogenesis, and capillary density. In vitro, rHDL increased key mediators involved in hypoxia-inducible factor-1α (HIF-1α) stabilization, including the phosphoinositide 3-kinase/Akt pathway, Siah1, and Siah2, and suppressed the prolyl hydroxylases (PHD) 2 and PHD3. rHDL rescued high glucose–induced impairment of tubulogenesis and vascular endothelial growth factor (VEGF) A protein production, a finding associated with enhanced phosphorylation of proangiogenic mediators VEGF receptor 2 and endothelial nitric oxide synthase. Siah1/2 small interfering RNA knockdown confirmed the importance of HIF-1α stability in mediating rHDL action. Lentiviral short hairpin RNA knockdown of scavenger receptor class B type I (SR-BI) in vitro and SR-BI−/− diabetic mice in vivo attenuated rHDL rescue of diabetes-impaired angiogenesis, indicating a key role for SR-BI. These findings provide a greater understanding of the vascular biological effects of HDL, with potential therapeutic implications for diabetic vascular complications.
- Subjects :
- 0301 basic medicine
Small interfering RNA
medicine.medical_specialty
Angiogenesis
Endocrinology, Diabetes and Metabolism
Biology
3. Good health
Small hairpin RNA
Vascular endothelial growth factor
Neovascularization
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
Endocrinology
chemistry
Internal medicine
Internal Medicine
medicine
Scavenger receptor
medicine.symptom
Wound healing
PI3K/AKT/mTOR pathway
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi...........14141cca6d4a6ae85aeaeca6669ca1cf