Beneficial effects of intramyocardial mesenchymal stem cells and VEGF₁₆₅ 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 VEGF165 (hVEGF165 ) plasmid on collagen remodelling in rats with furazolidone induced dilated cardiomyopathy (DCM). DCM was induced by furazolidone (0.3 mg/bodyweight (g)/day per gavage for 8 weeks). Rats were then divided into four groups: (i) PBS group (n = 18): rats received equal volume myocardial PBS injection; (ii) MSCs group (n = 17): 100 μl culture medium containing 10(5) MSCs were injected into four sites of left ventricular free wall (25 μl per site); (iii) GENE group (n = 18): pCMVen-MLC2v-EGFP-VEGF165 plasmid [5 × 10(9) pfu (0.2 ml)] were injected into four sites of left ventricular free wall (0.05 ml per site)] and (iv) MSCs+GENE group (n = 17): rats received both myocardial MSCs and pCMVen-MLC2v-EGFP-VEGF165 plasmid injections. After 4 weeks, cardiac function was evaluated by echocardiography. Myocardial mRNA expressions of type I, type III collagen and transforming growth factor (TGF)-β1 were detected by RT-PCR. The protein expression of hVEGF165 was determined by Western blot. Myocardial protein expression of hVEGF165 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-β1 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 hVEGF165 plasmid injection improves cardiac function possibly through down-regulating myocardial TGF-β1 expression and reducing the type I/III collagen ratio in this DCM rat model.