Diabetic cardiomyopathy (DCM) is a cardiovascular complication with no known cure. In this study, we evaluated the combination of ultrasound-targeted microbubble destruction (UTMD) and cationic microbubbles (CMBs) for cardiac S-adenosyl homocysteine hydrolase (SAHH) gene transfection as potential DCM therapy. Models of high glucose/fat (HG/HF)-induced H9C2 cells and streptozotocin-induced DCM rats were established. Ultrasound-mediated delivery using CMBs was a safe and noninvasive approach for spatially localized drug administration both and . Notably, overexpression increased cell viability and antioxidative stress and inhibited apoptosis of HG/HF-induced H9C2 cells. Likewise, UTMD-mediated delivery attenuated apoptosis, oxidative stress, cardiac fibrosis, and myocardial dysfunction in DCM rats. Activation of the AMPK/FOXO3/SIRT3 signaling pathway may be a key mechanism mediating the role of SAHH in regulating myocardial injury. Thus, UTMD-mediated transfection may be an important advancement in cardiac gene therapy for restoring ventricular function after DCM.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831940 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.108852 | DOI Listing |
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