BACKGROUNDMaintenance of normal cardiac function is controlled by the autonomic nervous system. In congestive heart failure (CHF), sympathetic nerve denervation is increasingly recognized. The sympathetic fiber density depends on the balance between neurotrophins and neural guidance molecules. Semaphorin 3A (sema3a), a secreted neural guidance factor, is a well characterized member of the newly found semaphorin family. It can induce sympathetic growth cone collapse and axon repulsion. We conducted this study to investigate cell sources of sema3a in the heart, the expression level of sema3a in CHF and discuss the possible role of sema3a in CHF.

METHODSRats were divided into four groups: 30 days control group rats, 30 days CHF rats, 60 days control group rats, 60 days CHF rats. The heart failure model was induced by injection of isoproterenol (ISO) 340 mg/kg continuously two days. All animals underwent echocardiography and haemodynamics measurements. Cardiac expression of sema3a was determined by real time polymerase chain reaction (RT-PCR) and Western blotting analysis. Immunohistochemical analysis was used to determine the cell source of sema3a in the heart.

RESULTSIsoproterenol induced 30 days and 60 days CHF rats displayed left ventricular dilation, systolic and diastolic function decrease. Sema3a was secreted by the cardiocytes and increased significantly in 30 days and 60 days CHF rats compared with the controls (RT-PCR: 30 days group: 0.32 ± 0.05 vs. 0.58 ± 0.06, P < 0.01; 60 days group: 0.34 ± 0.08 vs. 0.71 ± 0.07, P < 0.01. Western blotting: 30 days group: 0.25 ± 0.10 vs. 0.46 ± 0.10, P < 0.05; 60 days group: 0.29 ± 0.10 vs. 0.55 ± 0.16, P < 0.01. Immunohistochemical analysis: 30 days group: 2.91 ± 0.20 vs. 5.31 ± 0.30, P < 0.01; 60 days group: 2.94 ± 0.30 vs. 5.80 ± 0.30, P < 0.01).

CONCLUSIONSSema3a was expressed in the heart by cardiocytes. Increased expression of sema3a may partly account for sympathetic denervation in CHF; modulation of this pathway may prove beneficial in heart failure sympathetic remodeling.