Ultrasound‐targeted cationic microbubbles combined with the NFκB binding motif increase SDF‐1α gene transfection: A protective role in hearts after myocardial infarction

Abstract

Abstract Treatment of myocardial infarction (MI) remains a major challenge. The chemokine family plays an important role in cardiac injury, repair, and remodeling following MI, while stromal cell‐derived factor‐1 alpha (SDF‐1α) is the most promising therapeutic target. This study aimed to increase SDF‐1α expression using a novel gene delivery system and further explore its effect on MI treatment. In this study, two kinds of plasmids, human SDF‐1α plasmid (phSDF‐1α) and human SDF‐1α‐ nuclear factor κB plasmid (phSDF‐1α‐NFκB), were constructed and loaded onto cationic microbubble carriers, and the plasmids were released into MI rabbits by ultrasound‐targeted microbubble destruction. The transfection efficiency of SDF‐1α and the degree of heart repair were further explored and compared. In the MI rabbit models, transfection with phSDF‐1α‐NFκB resulted in higher SDF‐1α expression in peri‐infarct area compared with transfection with phSDF‐1α or no transfection. Upregulation of SDF‐1α was shown beneficial to these MI rabbit models, as demonstrated with better recovery of cardiac function, greater perfusion of the myocardium, more neovascularization, smaller infarction size and thicker infarct wall 1 month after treatment. Ultrasound‐targeted cationic microbubbles combined with the NFκB binding motif could increase SDF‐1α gene transfection, which would play a protective role after MI.

Keywords

• myocardial infarction
• nuclear factor κB
• stromal cell‐derived factor 1 alpha
• ultrasound targeted microbubble destruction