Angiogenesis inhibitor-specific hypertension increases the risk of developing aortic dissection

Biomed Pharmacother. 2023 Sep 16;167:115504. doi: 10.1016/j.biopha.2023.115504. Online ahead of print.ABSTRACTAortic dissection is an adverse event of angiogenesis inhibitors; however, the association between the drugs and aortic dissection is unclear. Therefore, we investigated if and how angiogenesis inhibitors increase the onset of aortic dissection using pharmacologically-induced aortic dissection-prone model (LAB) mice, cultured endothelial cells, and real-world databases, which is a novel integrated research approach. Disproportionality analysis was performed and calculated using the reporting odds ratio as a risk signal using a worldwide database of spontaneous adverse events to estimate the risk of adverse events. Angiogenesis inhibitors, but not other hypertension-inducing drugs, showed significant risk signals for aortic aneurysms and dissection. A retrospective cohort analysis using JMDC, a medical receipt database in Japan, showed that the history of atherosclerosis and dyslipidemia, but not hypertension, were significantly associated with the onset of aortic dissection during angiogenesis inhibitor medication administration. For in vivo studies, sunitinib (100 mg/kg/day) was administered to LAB mice. Sunitinib increased systolic blood pressure (182 mmHg vs. 288 mmHg with sunitinib; p＜0.01) and the incidence of aortic dissection (40% vs. 59% with sunitinib; p = 0.34) in mice. In vivo and in vitro studies revealed that sunitinib increased endothelin-1 expression ...

Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - September 18, 2023 Category: Drugs & Pharmacology Authors: Kaito Tsujinaka Yuki Izawa-Ishizawa Koji Miyata Toshihiko Yoshioka Kohei Oomine Honoka Nishi Masateru Kondo Syuto Itokazu Tatsumi Miyata Takahiro Niimura Maki Sato Fuka Aizawa Kenta Yagi Masayuki Chuma Yoshito Zamami Mitsuhiro Goda Keisuke Ishizawa Source Type: research