Beneficial Effects Of Intramyocardial Mesenchymal Stem Cells And Vegf(165) Plasmid Injection In Rats With Furazolidone Induced Dilated Cardiomyopathy

To explore the impact of myocardial injection of mesenchymal stem cells (MSCs) and specific recombinant human VEGF(165) (hVEGF(165)) plasmid on collagen remodelling in rats with furazolidone induced dilated cardiomyopathy (DCM). DCM was induced by furazolidone (0.3mg/bodyweight (g)/day per gavage for 8weeks). Rats were then divided into four groups: (i) PBS group (n=18): rats received equal volume myocardial PBS injection; (ii) MSCs group (n=17): 100l culture medium containing 10(5) MSCs were injected into four sites of left ventricular free wall (25l per site); (iii) GENE group (n=18): pCMVen-MLC2v-EGFP-VEGF(165) plasmid [5x109pfu (0.2ml)] were injected into four sites of left ventricular free wall (0.05ml per site)] and (iv) MSCs+GENE group (n=17): rats received both myocardial MSCs and pCMVen-MLC2v-EGFP-VEGF(165) plasmid injections. After 4weeks, cardiac function was evaluated by echocardiography. Myocardial mRNA expressions of type I, type III collagen and transforming growth factor (TGF)-1 were detected by RT-PCR. The protein expression of hVEGF(165) was determined by Western blot. Myocardial protein expression of hVEGF(165) was demonstrated in GENE and MSCs+GENE groups. Cardiac function was improved in MSCs, GENE and MSCs+GENE groups. Collagen volume fraction was significantly reduced and myocardial TGF-1 mRNA expression significantly down-regulated in both GENE and MSCs+GENE groups, collagen type I/III ratio reduction was more significant in MSCs+GENE group than in MSCs or GENE group. Myocardial MSCs and hVEGF(165) plasmid injection improves cardiac function possibly through down-regulating myocardial TGF-1 expression and reducing the type I/III collagen ratio in this DCM rat model.