Xu Jiayi, Lin Junling, Gan Haojian, He Qingjian, Wang WenJuan, Liu Yuanhua
School of Medicine, Huzhou University, Huzhou, China.
Department of Breast and Thyroid Surgery, First Affiliated Hospital of Huzhou University, Huzhou, China.
Front Pharmacol. 2025 May 15;16:1585061. doi: 10.3389/fphar.2025.1585061. eCollection 2025.
Bruton's tyrosine kinase inhibitors (BTKis) have made substantial impacts on the treatment of B-cell malignancies like chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Therapeutic benefits aside, the clinical use of BTKis comes with several side effects, of which hypertension (HTN) is quite common and serious and of significant clinical concern. The present article will discuss the mechanisms by which the use of BTKis causes hypertension and outline strategies for managing the condition within the clinic. Studies indicate that using BTKis interferes with BTK's central role within the B-cell receptor (BCR) signaling cascade and impacts multiple downstream signaling pathways like PI3K/Akt, MAPK, and NF-κB. These changes contribute to endothelial dysfunction, increased oxidative stress, and vascular constriction, all of which are implicated in the development of hypertension. Of special concern is that oxidative stress (OS) is directly related to decreased endothelial nitric oxide (NO) production, a finding that becomes particularly relevant during the initiation of BTKi therapy. Also, BTKis affect vascular development and tone regulation by activating the Notch and RhoA/ROCK pathways, leading to increased vasoconstriction and the advancement of hypertension. In light of the possibility that BTKi-induced hypertension might jeopardize treatment tolerability and patient outcomes, this review proposes a multimodal management of the condition, including careful monitoring of blood pressure, individualized antihypertensive treatment, and possible modifications of the dosing of BTKis. Future investigations should look into the specific molecular mechanisms underpinning the development of hypertension due to BTKis as well as the effects of various antihypertensive regimens on the improvement of the cardiovascular profile of affected individuals.
布鲁顿酪氨酸激酶抑制剂（BTKis）对慢性淋巴细胞白血病（CLL）和小淋巴细胞淋巴瘤（SLL）等B细胞恶性肿瘤的治疗产生了重大影响。除了治疗益处外，BTKis的临床应用还伴随着几种副作用，其中高血压（HTN）相当常见且严重，是临床关注的重点。本文将讨论使用BTKis导致高血压的机制，并概述在临床中管理该病症的策略。研究表明，使用BTKis会干扰BTK在B细胞受体（BCR）信号级联反应中的核心作用，并影响多个下游信号通路，如PI3K/Akt、MAPK和NF-κB。这些变化会导致内皮功能障碍、氧化应激增加和血管收缩，所有这些都与高血压的发生有关。特别值得关注的是，氧化应激（OS）与内皮一氧化氮（NO）生成减少直接相关，这一发现在BTKi治疗开始时尤为重要。此外，BTKis通过激活Notch和RhoA/ROCK通路影响血管发育和张力调节，导致血管收缩增加和高血压进展。鉴于BTKi诱导的高血压可能会危及治疗耐受性和患者预后，本综述提出了对该病症的多模式管理，包括仔细监测血压、个体化抗高血压治疗以及可能调整BTKis的剂量。未来的研究应深入探究BTKis导致高血压的具体分子机制，以及各种抗高血压方案对改善受影响个体心血管状况的作用。
