PB1338 - The therapeutic potential of NAMPT in protecting against chronic thromboembolic pulmonary hypertension

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Lu Sun, doctoral student

doctoral student
Chinese Academy of Medical Sciences & Peking Union Medical College; China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)

Co-Author(s)

JL

Jixiang Liu

postdoctor
Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases; Peking University Health Science Center
Beijing, Beijing, China (People's Republic)
PY

Peiran Yang

professor
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences
Beijing, Beijing, China (People's Republic)
Zhenguo Zhai, MD,PhD

professor
China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China
Beijing, Beijing, China (People's Republic)

Background: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a severe cardiovascular condition where the development of neointima in the pulmonary arteries plays a pivotal role in disease progression. Recent research has suggested a potential link between NAMPT (Nicotinamide Phosphoribosyltransferase), involved in metabolism and aging processes and the occurrence and progression of CTEPH. However, the exact mechanisms of NAMPT in CTEPH remain unclear.

Aims: This study aimed to investigate the expression of NAMPT and aging-related genes in CTEPH patients to gain deeper insights into the role of NAMPT in the pathogenesis of CTEPH.

Methods: Plasma samples were collected from CTEPH patients and healthy controls, along with smooth muscle tissues obtained during pulmonary endarterectomy（PEA） procedures. mRNA expression levels of NAMPT and aging-related genes were analyzed using real-time quantitative PCR (qPCR). Furthermore, we conducted in vitro experiments using FK866, a NAMPT inhibitor, to study the regulatory effect of NAMPT on smooth muscle proliferation.

Results: Our findings revealed a significant decrease in NAMPT expression in the plasma of CTEPH patients compared to healthy controls(N=28,P＜0.01). In isolated smooth muscle tissue from CTEPH patients, we observed a substantial reduction in NAMPT expression（N=4,P＜0.01） and an increase in the expression of aging-related genes,such as P16（N=3,P＜0.0001），P21（N=3,P＜0.01），H2AX（N=3,P＜0.01）. Furthermore, we have demonstrated that smooth muscle hyperplasia exists in patients with CTEPH(N=3,P＜0.01).CTEPH smooth muscle exhibited excessive proliferation, and FK866（N=3,P＜0.001）, which inhibits NAMPT activity（N=3,P＜0.05）, exacerbated smooth muscle overgrowth. Conversely, increasing NAMPT expression effectively suppressed smooth muscle proliferation.

Conclusion(s): In summary, our study suggests that reduced NAMPT expression in CTEPH patients, coupled with elevated expression of aging-related genes, may be associated with the pathogenesis of CTEPH and neointimal formation.