The therapeutic potential of NAMPT in protecting against chronic thromboembolic pulmonary hypertension

<bold>Background:</bold> Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a severe disease, which the development of neointima in the pulmonary arteries plays a pivotal role. It was suggested a potential link between NAMPT (Nicotinamide Phosphoribosyltransferase), involved in aging processes and the occurrence and progression of CTEPH. However, the exact mechanisms of NAMPT in CTEPH remain unclear. <bold>Methods:</bold> Plasma samples were collected from CTEPH patients and healthy controls, as well as smooth muscle cells obtained during pulmonary endarterectomy (PEA). real-time quantitative PCR (qPCR) and western blot were used to analyze the expression levels of NAMPT and age-related genes in smooth muscle cells. In addition, NAMPT inhibitor FK866,isstudy the regulatory effect of NAMPT on smooth muscle proliferation. <bold>Result:</bold> Plasma NAMPT expression was significantly reduced in CTEPH patients compared to healthy controls (Figure G,N=28,P＜0.01). In the α-SMA positive regions of smooth muscle in PEA tissues, we observed a significant decrease in NAMPT expression (Figure A,C,D,N=4,P＜0.01), aging related genes such as P16(N=3,P＜0.0001), P21(N=3,P＜0.01) increased in expression. Furthermore, we have demonstrated CTEPH smooth muscle cell hyperplasia(Figure E,N=3,P＜0.01), inhibition of NAMPT activity of FK866(Figure E, N=3,P＜0.001) aggravated smooth muscle hyperplasia (Figure E,N=3,P＜ 0.05). On the contrary, increasing the expression of NAMPT can effectively inhibit smooth muscle proliferation(Figure E,N=3,P＜0.05). <bold>Conclusion:</bold> In summary, reduced NAMPT expression in CTEPH patients, coupled with elevated expression of aging-related genes, may be associated wth pathogenesis of CTEPH.