OBJECTIVES: The purpose of this study was to evaluate the effect of CX37 gene silence on myocardial fractional flow reserve (FFR). METHODS: A total of 90 male pigs were randomly divided into saline, mock and 3 different doses (5, 10 and 20 mu l) of CX37 viral suspension groups that could induce coronary plaque formation with high-fat diet. After performing myocardial FFR by intravascular ultrasound, different doses of CX37 viral suspension, saline and mock small interfering RNA (siRNA) were transfected into the related coronary. The FFR, the myocardial enzymes and the cardiac structures and functions of the pigs were detected at baseline, 4th, 8th and 12th week after transfection, respectively. RESULTS: Repeated measures analysis of variance comparison showed that the difference in the FFR among the 5 groups was statistically significant (F = 27.0, P < 0.01). Post hoc analysis showed that FFR were highest in the siRNA CX37 group (20 ml), followed by the siRNA CX37 group (10 ml) and the siRNA CX37 group (5 ml), and lowest in the mock and saline groups. Left ventricular end-diastolic diameter was significantly smaller and ejection fraction was obviously higher in the 3 siRNA CX37 groups compared with the untreated groups. ONCLUSIONS: Our study showed that FFR levels increased along with decreased doses of siRNA CX37 lentivirus, indicating that siRNA CX37 lentivirus may reduce the risk of coronary atherosclerosis and provide a potential approach to treat coronary heart disease.