Abstract：
PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40-0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.
摘要：
据报道,PDE5抑制剂在调节脂质代谢和减少心力衰竭(HF)两者中起保护作用。本研究旨在通过结合基于人群的研究和动物模型的证据来阐明PDE5抑制剂对高脂血症相关HF的有效性。全国队列研究发现，与使用前列地尔的患者相比，诊断后使用PDE5抑制剂与HF风险显着降低相关。尤其是在高脂血症患者中(校正后的HR=0.56,95%CI=0.40-0.78).在动物模型中,西地那非显著恢复了AAB手术诱导的心脏结构和功能，以及通过降低ALT水平逆转HFD诱导的肝功能障碍和改善高脂血症，AST和血清脂质。脂质组学分析确定了西地那非给药涉及的四种脂质代谢物，包括FA16:3、LPCO-18:1、DG24:0_18:0和SE28:1/20:4。这项研究揭示了PDE5抑制剂对高脂血症HF的保护作用。表明如果这些发现可以在临床试验中得到进一步证实，则有可能被用作高脂血症患者HF预防的辅助药物。
