Abstract
The purpose of this study was to evaluate the protective effect of acidic fibroblast growth factor targeted mediated by novel nanoparticles–cationic lipid microbubbles complex (aFGF–NP + CPMBs) combined with ultrasound targeted microbubble destruction (UTMD)on doxorubicin–induced heart failure (HF)and its mechanism. Heart failure rats induced by intraperitoneal injection with doxorubicin (DOX) to achieve cummulative dose of 15mg/kg for continuous 6 weeks showed left ventricular dysfunction, seriously oxidative stress, cardiomyocyte apoptosis, and decrease of myocardial vascular density. In contrast, aFGF–NP + CPMBs combined with UTMD therapy (3ug/kg, caudal vein injection, twice a week, 6weeks)prominently ameliorated left ventricular dysfunction by increased ejection fraction (EF) and fractional shortening (FS), decreased brain natriuretic peptide (BNP); strengthened the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA; exerted the effect of anti–cardiomyocyte apoptosis and promotion angiogenesis by inhibited Bax expression and increased Bcl–2 expression and platelet endothelial cell adhesion molecule (CD31) expression. Taken together, the research suggested that aFGF targeted mediated by novel nanoparticles–cationic lipid microbubbles complex combined with UTMD should be a promising targeted treatment for heart failure.
Highlights
In recent years, ultrasound targeted microbubble destruction (UTMD)as a new non–invasive drug/gene–targeted delivery technology, (Tian et al, 2017) has attracted more and more attention
Our research results have demonstrated the effect of Acidic fibroblast growth factor (aFGF) targeted mediated by novel nanoparticles-cationic lipid microbubbles combined with UTMD in the therapy of heart failure as follows: 1) it can attenuate doxorubicin-induced heart failure and improve cardiac dysfunction; 2) it increases the activity of superoxide dismutase and decreases the formation of malondialdehyde, down-regulates the expression of Bax and up-regulates the expression of Bcl-2 in cardiac myocyte, inhibits cardiomyocyte oxidative stress and apoptosis in heart failure; 3) it promotes angiogenesis in cardiac tissue during heart failure via increasing the expression of CD31; proposing a novel mechanism for anti-heart failure cardioprotection of aFGF targeted mediated by novel nanoparticles-cationic lipid microbubbles combined with UTMD
The main pathological features of heart failure are concentric or eccentric myocardial hypertrophy, decreation of cardiomyocytes caused by necrosis or apoptosis, myocardial fibrosis, disturbance of energy production, and reduction of capillary density in hypertrophic myocardium (Goldenthal, 2016).The above pathological changes lead to myocardial remodeling, which further leads to the decrease of myocardial compliance, that is, the increase of stiffness, which affects the systolic and diastolic function of the myocardium (Ruan et al, 2018)
Summary
Ultrasound targeted microbubble destruction (UTMD)as a new non–invasive drug/gene–targeted delivery technology, (Tian et al, 2017) has attracted more and more attention. Under the action of diagnostic or therapeutic ultrasound, the cavitation effect and mechanical effect of ultrasonic microbubble blasting cause temporary open pores on the local endothelial cell membrane and capillaries, through which drugs/genes can be diffused into the tissue to achieve targeted drug or gene delivery and enhances the uptake rate of tissue and therapeutic effect of the drugs. It can collect real–time images and data information of specific tissue structure and function changes. Great progress has been made in relieving the symptoms of heart failure, the fatality rate of heart failure is still very high, so there is still an urgent need to develop innovative treatment strategies for increasing the therapeutic effect of heart failure
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