Tyagi Samuel C, Ito Sohei, Hubbuch Jacob C, Franklin Michael K, Howatt Deborah A, Lu Hong S, Daugherty Alan, Sawada Hisashi
Saha Cardiovascular Research Center, College of Medicine University of Kentucky.
Saha Aortic Center, College of Medicine University of Kentucky.
bioRxiv. 2025 Mar 27:2025.03.24.645113. doi: 10.1101/2025.03.24.645113.
Thoracic aortopathies are life-threatening diseases including aneurysm, dissection, and rupture. Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide concentrations. Recent studies report the influences of cilostazol, a PDE3 inhibitor, and sildenafil, a PDE5 inhibitor, on abdominal aortic aneurysm formation. However, their impacts on thoracic aortopathy remain unknown. In this study, we investigated whether cilostazol and sildenafil affect thoracic aortopathy induced by β-aminopropionitrile (BAPN) administration in mice. Bulk RNA sequencing analysis revealed that BAPN administration upregulated transcription in the ascending aorta and in both ascending and descending regions before thoracic aortopathy formation. Next, we tested the effects of cilostazol or sildenafil on BAPN-induced thoracic aortopathy. BAPN-administered mice were fed a diet supplemented with either cilostazol or sildenafil. Mass spectrometry measurements determined the presence of cilostazol or sildenafil in the plasma of mice fed drug-supplemented diets. However, neither drug altered BAPN-induced aortic rupture nor aneurysm formation and progression. These results provide evidence that cilostazol and sildenafil did not influence BAPN-induced thoracic aortopathy in mice.
胸主动脉疾病是包括动脉瘤、夹层和破裂在内的危及生命的疾病。磷酸二酯酶（PDEs）调节细胞内环核苷酸浓度。最近的研究报道了磷酸二酯酶3抑制剂西洛他唑和磷酸二酯酶5抑制剂西地那非对腹主动脉瘤形成的影响。然而，它们对胸主动脉疾病的影响尚不清楚。在本研究中，我们调查了西洛他唑和西地那非是否会影响β-氨基丙腈（BAPN）诱导的小鼠胸主动脉疾病。批量RNA测序分析显示，在胸主动脉疾病形成之前，给予BAPN可上调升主动脉以及升主动脉和降主动脉区域的转录。接下来，我们测试了西洛他唑或西地那非对BAPN诱导的胸主动脉疾病的影响。给给予BAPN的小鼠喂食补充了西洛他唑或西地那非的饮食。质谱测量确定了喂食补充药物饮食的小鼠血浆中存在西洛他唑或西地那非。然而，两种药物均未改变BAPN诱导的主动脉破裂、动脉瘤形成和进展。这些结果证明西洛他唑和西地那非不会影响BAPN诱导的小鼠胸主动脉疾病。
