Ultrasound targeted microbubbles destruction-mediated the Ang1 gene transfection improves left ventricular mechanical synchrony during the progression of myocardial infarction in canines

Objective To evaluate the left ventricular synchrony after myocardial infarction (MI) by ultrasound targeted microbubbles destruction (UTMD)-mediated angiogenin 1 (Ang1) gene transfection in canine. Methods Twenty-one dogs were divided into three groups (n=7 in each group): ①control group (healthy dogs); ②MI group (MI dogs without treatment); ③UTMD group (MI dogs with UTMD treatment). One month later, the size and systolic function of heart were measured by echocardiography. The synchronization parameters derived from two dimensional-speckle tracking imaging(2D-STI) included the standard deviation and maximum difference of time to peak strain for all left ventricular segments (Tls-SD, Trs-SD, Tcs-SD, Tls-Dif, Trs-Dif and Tcs-Dif). CD31 and α-SMA were applied for quantifying capillary and arteriolar density. The Ang1, SERCA2a and PLB protein were detected by Western blotting. Results ①One month later, the conventional ultrasonic parameters were compared among three groups, the LVEDD, LVESD and E/e′ increased and LVEF, e′ and E/A reduced in MI group than those in control group, all of them partially recovered in UTMD group than those in MI group, but were still lower than those in control group (P 0.05); ③The immunohistochemistry showed the higher blood vessel density in UTMD group than that in MI group(P<0.05); ④The relative quantity of Ang1 was significantly higher in UTMD group. The relative quantity of SERCA2a protein was lower in MI group than that in control group, increased in UTMD group, the trend of PLB was contrary to it. The differences were statistically significant (all P<0.05). Conclusions The UTMD-mediated Ang1 gene transfection can promote angiogenesis after MI, reverse left ventricular remodeling and improve left ventricular synchrony. The myocardial synchrony may be related to the expression of calcium ions key protein SERCA2a and PLB. Key words: Sonication; Transfection; Myocardial infarction; Synchrony; Speckle tracking imaging