Abstract
Abstract We129: Endothelium-Targeted MiR-122 Inhibition Improves Vascular Endothelial Function In a High-Fat Diet Fed mice
Circulation research, Vol.135(Suppl_1)
08/02/2024
DOI: 10.1161/res.135.suppl_1.We129
Abstract
Abstract only Background: MicroRNA-122-5p (miR-122), a liver-specific miR, levels are increased in the blood during obesity and diabetes and is taken-up by the extra-hepatic tissues including vascular endothelium. Despite miR-122’s role in maintaining hepatic homeostasis, its uptake (from circulation) by other tissues disrupts their function and increases the risk of cardiovascular disorders. Hence, inhibiting extra-hepatic miR-122 is a viable approach to mitigate vascular disorders associated with diabetes. Hypothesis: Endothelium-targeted miR-122 inhibitor selectively targets miR-122 in endothelial cells and improves vascular endothelial function in high-fat-diet (HFD) fed pre-diabetic mice. Methods: To selectively inhibit miR-122 in the endothelial cells, we synthesized gamma-peptide nucleic acid miR-122 inhibitor (γP-122 I) tagged with vascular cell adhesion molecule 1 (VCAM1) targeted peptide (e-γP-122 I). The purity was assessed using HPLC. Pre-diabetic condition was induced by feeding mice with a HFD (for 8 weeks) and e-γP-122-I was injected to the HFD-fed mice (2 weeks after dietary intervention; 5 mg/kg/day, i.p., 6 weeks). MiR-122 expression was measured by real-time PCR. The vascular endothelial function was assessed by determining endothelium-dependent and independent relaxation of phenylephrine-induced precontracted aortic rings. Results were expressed as mean ± s.e.m. Results: The e-γP-122-I was >95% pure. The HFD-fed mice show higher levels of serum and aortic miR-122 expression and impaired vascular endothelial function. e-γP-122-I treatment selectively inhibited aortic miR-122 expression while it has no effect on other organs (heart, kidney etc.) and improved vascular endothelial function and inflammation. Conclusions: e-γP-122-I selectively inhibits miR-122 in the endothelium and improves endothelial function in pre-diabetic mice.
Details
- Title: Subtitle
- Abstract We129: Endothelium-Targeted MiR-122 Inhibition Improves Vascular Endothelial Function In a High-Fat Diet Fed mice
- Creators
- Ravinder Gaddam - University of IowaKarishma Dhuri - University of ConnecticutMounika Pathuri - University of ConnecticutVeda Amalkar - University of IowaYOUNG-RAE Kim - University of IowaJulia Jacobs - University of IowaVeeresh Kumar Sali - University of IowaKrishna Nakuluri - University of IowaKaikobad Irani - University of IowaRaman Bahal - University of ConnecticutAjit Vikram - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.135(Suppl_1)
- DOI
- 10.1161/res.135.suppl_1.We129
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/02/2024
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984736613102771
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