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 real-time myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×β 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.

Highlights

  • With the development of the economy and society, as well as changes in people’s dietary habits and lifestyles, the incidence of diabetes mellitus (DM) is increasing annually, and the age of onset has become younger

  • The results showed that the myocardial ultrastructure of DM rats was improved after different forms of FGF1 prevention, but compared with other forms of prevention, FGF1-nlip combined with ultrasound-targeted microbubble destruction (UTMD) technology had the most obvious preventive effect

  • The rat model of DM was established by intraperitoneal injection of STZ

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Summary

Introduction

With the development of the economy and society, as well as changes in people’s dietary habits and lifestyles, the incidence of diabetes mellitus (DM) is increasing annually, and the age of onset has become younger. There are approximately 425 million DM patients worldwide in 2017, and the number is expected to reach 700 million by 2045 (Cho et al, 2018). Diabetes cardiomyopathy (DCM) is a series of changes in the myocardial structure and function caused by DM (Borghetti et al, 2018; Parim et al, 2019) that are not related to coronary atherosclerosis, hypertension, and valvular heart disease (Rubler et al, 1972). DCM has been identified as the main cause of heart failure and death in patients with DM (Evangelista et al, 2019; Gulsin et al, 2019; Zamora and Villena, 2019). Early detection and timely intervention therapy are of great significance for the prognosis of DM patients

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