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Autologous Endothelial Progenitor Cell-Seeding Technology and Biocompatibility Testing For Cardiovascular Devices in Large Animal Model
Published on: September 9, 2011
Engineered endothelial cells targeting and dihydrotanshinone I loaded bacterial extracellular vesicles for
Rong-Rong Zhu1, Xue-Liang Zhou2, Yan-Wei Liu1
1Department of Cardiology The Affiliated Hospital of Jiangxi University of Chinese Medicine Nanchang China.
Insights
Engineered endothelial cell-targeted extracellular vesicles loaded with dihydrotanshinone I (DHT) show promise for treating atherosclerosis (AS). This novel therapy effectively reduced AS in mice, offering a potential alternative to traditional treatments.
Area of Science:
- Cardiovascular Research
- Nanomedicine
- Cell Biology
Background:
- Atherosclerosis (AS) is a complex cardiovascular disease involving endothelial dysfunction, dyslipidemia, and inflammation.
- Current treatments like statins have limitations in efficacy and side effects.
- Novel therapeutic strategies are needed to combat AS effectively.
Purpose of the Study:
- To investigate the anti-atherosclerotic effects of engineered endothelial cell-targeting probiotic extracellular vesicles loaded with dihydrotanshinone I (EC-BEVsDHT).
- To explore the molecular mechanisms underlying the therapeutic potential of EC-BEVsDHT in AS treatment.
- To evaluate the efficacy and safety of EC-BEVsDHT as a novel therapeutic strategy for AS.
Main Methods:
- Characterization of EC-BEVsDHT using transmission electron microscopy and nanoparticle tracking analysis.
- Confirmation of ECs-targeting peptide VSSSTPR expression via HPLC-MS/MS.
- In vitro assessment of EC-BEVsDHT effects on oxidized LDL-induced HUVECs injury.
- In vivo evaluation of EC-BEVsDHT in Apolipoprotein E-deficient (ApoE-/-) mice models of AS.
Main Results:
- EC-BEVsDHT exhibited spherical morphology and appropriate particle size.
- The ECs-targeting peptide VSSSTPR was successfully incorporated into the vesicles.
- EC-BEVsDHT significantly attenuated oxidized low-density lipoprotein-induced HUVECs injury in vitro.
- EC-BEVsDHT demonstrated a significant decrease in atherosclerosis progression in ApoE-/- mice in vivo.
Conclusions:
- Engineered endothelial cell-targeting probiotic extracellular vesicles loaded with dihydrotanshinone I (EC-BEVsDHT) represent a promising novel therapeutic approach for atherosclerosis.
- This strategy effectively reduces AS in preclinical models, suggesting potential advantages over conventional treatments.
- EC-BEVsDHT offer a potential new avenue for managing cardiovascular disease with improved safety and efficacy.
Abstract:
Atherosclerosis (AS) is a complex cardiovascular disease characterized by endothelial dysfunction, dyslipidemia, and immune-inflammatory responses, leading to arterial plaque formation and potentially fatal complications such as myocardial infarction and stroke. Traditional treatments, such as statins, often pose challenges due to their side effects and limited efficacy. In this study, we explore a novel therapeutic approach utilizing engineered endothelial cells (ECs) targeting probiotic extracellular vesicles loaded with dihydrotanshinone I (DHT) (EC-BEVsDHT), a bioactive compound derived from Danshen (Salvia miltiorrhiza Bunge). With the characterization of EC-BEVsDHT by transmission electron microscope and nanoparticle tracking analysis, EC-BEVsDHT exhibited typical spherical morphology and particle size distribution. High-performance liquid chromatography coupled with tandem mass spectrometric confirmed the expression of the ECs-targeting peptide VSSSTPR in EC-BEVsDHT and EC-BEVsDHT. We further investigated the anti-atherosclerotic effects and molecular mechanisms of EC-BEVsDHT on human umbilical vein endothelial cells (HUVECs) and Apolipoprotein E-deficient (ApoE-/-) C57BL/6J mice. We found that EC-BEVsDHT attenuated oxidized low-density lipoprotein induced HUVECs injury in vitro and decreased AS in ApoE-/- mice in vivo. Our findings suggest that EC-BEVsDHT hold promise as a safe and effective therapeutic strategy for AS, offering potential advantages over traditional treatments.

