GW24-e2448 Knockdown of farnesyl pyrophosphate synthase prevents cardiac fibrosis of spontaneously hypertensive rats in vivo

Objectives Previous studies show farnesyl pyrophosphate synthase (FPPS) inhibitor prevents cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II). In this study, we examined the effect of lentivirus against FPPS on fibrosis in spontaneously hypertensive rats (SHRs). Methods Scrambled control lentivirus or lentivirus against FPPS was injected into the left ventricular wall of WKYs or SHRs. FPPS expression and cardiac fibrosis marker gene, including collagen I and collagen III, were measured by qRT-PCR. Cardiac index of animal models was evaluated by echocardiogram. Results First, We demonstrated that FPPS expression was down-regulated both in WKYs and SHRs. In addition, in vivo gene transfer also attenuated fibrotic responses as indexed by heart weight/body weight (HW/BW), left ventricular weight/body weight (LVW/BW). Meanwhile, the expression of collagen I and collagen III were both reduced. Conclusions FPPS knockdown prevents impaired cardiac extracellular matrix deposition in spontaneously hypertensive rats and this effect might be via collagen I and collagen III reduction.