Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound

Abstract

Acidic fibroblast growth factor (FGF1) has great potential in preventing diabetic cardiomyopathy. This study aimed to evaluate the preventive effect of FGF1-loaded nanoliposomes (FGF1-nlip) combined with ultrasound-targeted microbubble destruction (UTMD) on diabetic cardiomyopathy (DCM) using ultrasound examination. Nanoliposomes encapsulating FGF1 were prepared by reverse phase evaporation. DM model rats were established by intraperitoneal injection of streptozotocin (STZ), and different forms of FGF1 (FGF1 solution, FGF1-nlip, and FGF1-nlip+UTMD) were used for a 12-week intervention. According to the transthoracic echocardiography and velocity vector imaging (VVI) indexes, the LVEF, LVFS, and VVI indexes (Vs, Sr, SRr) in the FGF1-nlip+UTMD group were significantly higher than those in the DM model group and other FGF1 intervention groups. From the realtime myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×b showed significant differences from the DM model group and other FGF1 intervention groups. Cardiac catheter hemodynamic testing, CD31 immunohistochemical staining, and electron microscopy also confirmed the same conclusion. These results confirmed that the abnormalities, including myocardial dysfunction and perfusion impairment, could be suppressed to different extents by the twice weekly FGF1 treatments for 12 consecutive weeks (free FGF1, FGF1-nlip, and FGF1-nlip+UTMD), with the strongest improvements observed in the FGF1-nlip+UTMD group. In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM.

Ultrasound-targeted microbubble destruction promotes myocardial angiogenesis and functional improvements in rat model of diabetic cardiomyopathy

“…Accumulating evidence has demonstrated a progressive reduction of the microvasculature and an impaired angiogenic response to chronic ischemia with the development of diabetes [ 8 ]. Recently, low-intensity ultrasound in combination with microbubbles has been shown to stimulate endogenous vascular growth factor, inducing angiogenesis, used in ischemic diseases [ 5 , 21 , 22 ]. As gas-filled colloidal materials, SnonVue MBs consisted of an inert gas core and shell composition of phospholipid, polymer with a typical mean diameter of 2.5 μm.…”

“…All animal experiments in this study were approved by the Animal Care and Use Committee of Xinxiang Medical College and conducted by the “Guide for the Care and Use of Laboratory Animals” from the National Institutes of Health. Sprague- Dawley (SD) rats were widely used as an animal model for studying diabetes mellitus (DM), which were suitable for the evaluation of cardiac function [ 5 , 6 , 12 , 13 , 17 ]. Male rats (7–8 weeks, 160–180 g) were provided by the Experimental Animal Center of Zhengzhou University.…”

“…*Correspondence: 342354073@qq.com † Xijun Zhang and Xinqiao Tian equally contribute to this work; they both are listed as the co-first authors 1 Department of Ultrasonography, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Henan University People's Hospital, NO. 7 Weiwu Road, Zhengzhou 450003, Henan, China Full list of author information is available at the end of the article special symptoms in the early stage and lack of specialized treatment strategies [3][4][5][6]. Therefore, reveal the subtle changes of cardiac mechanics are important for patient management and intervention.…”

“…However, previous studies have reported the delivery approach of proteins and genes, including intracoronary, intrapericardial or myocardial administration, are inefficient and high risk that prevent its clinical applications. At the moment, ultrasound-targeted microbubble destruction (UTMD) has been developed as a noninvasive and target specific method in angiogenesis therapy of cardiovascular disease [ 5 , 12 , 13 ].…”

aFGF Targeted Mediated by Novel Nanoparticles-Microbubble Complex Combined With Ultrasound-Targeted Microbubble Destruction attenuates Doxorubicin-Induced Heart Failure via Anti-Apoptosis and Promoting Cardiac Angiogenesis

“…UTMD has been proved to be a promising method for targeting drug/gene transmission and treatment of many diseases, including diagnosis and treatment of malignant tumor, ( Sun et al, 2020 ) Parkinson, ( Lin et al, 2020 ) brain ischaemic, diabetic cardiomyopathy, ( Zheng et al, 2019 ) atherosclerosis, ( Yang et al, 2019 ) transplantation rejection ( Liu et al, 2019a ).…”