ABSTRACT
Objective To evaluate the effect of ultrasound guided via chest puncture injection and ultrasound targeted microbubble destruction(UTMD) mediated the angiogenin 1 (Ang1) gene therapy in myocardial infarction (MI) canines.Methods Thirty nine dogs were divided into three groups (each group 13 dogs):① MI group (MI dogs without treatment);② intravenous injection group (MI dogs with intravenous injection and UTMD treatment);③ myocardial injection group (MI dogs with myocardial injection and UTMD treatment).Four weeks later,the safety and incidence of complications were compared.The dimensions and systolic function of left ventricular were measured by echocardiography.The percentage of collagen fiber was assessed by Masson.CD31 was applied for quantifying capillary density.The Ang1 protein was detected by Western blotting.Results ①The survival and complications showed no significant difference among the 3 groups(allP ＞0.05).②Compared with MI group,the left ventricular end systolic dimension (LVESD)reduced and the left ventricular ejection fraction (LVEF) increased in intravenous injection group;the left ventricular end-diastolic dimension (LVEDD) and LVESD were both reduced in myocardial injection group,the LVEF was increased significantly(all P ＜0.05).③ The immunohistochemistry showed lower collagen fiber percentage and higher blood vessel density in myocardial injection group than those in the other groups(P ＜0.05).④The relative quantity of Ang1 was significantly higher in myocardial injection group than those of the other groups.The differences were statistically significant (P ＜0.05).Conclusions The combination of ultrasound guided via chest puncture injection and UTMD is a safe and effective method for gene transfection.It mediates Ang1 gene transfection that can promote angiogenesis after MI and improve left ventricular systolic function.
ABSTRACT
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 ① One 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);②The left ventricular synchrony parameters of Tls-SD,Tls-Dif and Trs-SD showed significant differences among the three groups(P ＜0.05),the degree of dyssynchrony increased in MI group than control group,they were lower in UTMD group than those in MI group.The Tcs-SD,Tcs-Dif and Trs-Dif showed no significant difference among three groups (P ＞ 0.05);③ The 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.