[Phospholamban antisense RNA transfer attenuates post-infarction remodeling and preserves cardiac functions].

ABSTRACT

OBJECTIVE: To investigate whether the gene transfer of phospholamban antisense RNA could inhibit remodeling and preserve cardiac function after myocardial infarction. METHODS: Wistar rats received a ligation of left coronary with a direct intramyocardial injection of phospholamban antisense RNA eukaryote vector PcDNA4-asPLB. The cardiac function, hemodynamics and ventricular geometry of three groups (shame, saline injection and PcDNA4-asPLB injection) were studied by echocardiography and left ventricle hemodynamic recording. The levels of phospholamban (PLB) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) were analyzed by Western blot and the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) examined by RT-PCR. The histological study was performed to evaluate the collage content and cardiomyocyte fiber size. RESULTS: The PcDNA4-asPLB injection group had significantly better systolic cardiac function and diastolic function [LVEF (39.4 +/- 7.8)% vs (30.9 +/- 7.4)%, P < 0.05; dp/dt Max (1545 +/- 127) mm Hg x s(-1) vs (1172 +/- 91) mm Hg x s(-1), P < 0.05)]. Compared with saline injection, the PLB expression was inhibited by 50% in PcDNA4-asPLB injection group (PLB/beta-actin ratio, 0.28 +/- 0.07 vs 0.57 +/- 0.11, P < 0.05) and the function of SERCA2a was enhanced [(1.47 +/- 0.21) micromol x min(-1) x g(-1) protein vs (0.34 +/- 0.13) micromol x min(-1) x g(-1) protein, P < 0.05]. The expressions of ANP and BNP in the saline injection group were elevated as compared to those in the PcDNA4-asPLB injection group. Histological study also showed that the collage density and the cardiomyocyte fiber size in the saline injection group were worse than those in the PcDNA4-asPLB injection group. CONCLUSION: Intramyocardial injection of phospholamban antisense RNA eukaryote vector PcDNA4-asPLB after myocardial infarction results in PLB expression inhibition, attenuates ventricular remodeling and improves systolic and diastolic cardiac functions.