Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Hypertension. 2013 Aug;62(2):415-25. doi: 10.1161/HYPERTENSIONAHA.111.01076. Epub 2013 Jun 3.
Human β-defensin 2 (HBD2) is a cysteine-rich cationic antimicrobial peptide known for its important role in innate immune system. Intensive studies have demonstrated its antimicrobial and chemotactic activities in vitro. In this study, ELISA analysis showed that HBD2 was significantly downregulated in sera of patients with hypertension. It relaxed vessel smooth muscle by acting on the major regulatory pathways, contributing to vessel smooth muscle contraction. Electrophysiology analysis indicated that HBD2 acted as an opener of large-conductance Ca(2+)-activated potassium (BKCa)-mSlo+hβ1 channels and increased BKCa currents. Mutation analysis revealed that HBD2 activated BKCa-mSlo+hβ1 channels via interacting with Leu41 and Gln43 of β1-loop. In vivo experiments suggested that HBD2 at 4 × to 6 × of physiological concentration exerted hypotensive effect in monkeys significantly, whereas the selective blocker of BKCa channels, Paxilline, inhibited the effect. HBD2 is the first peptide opener of BKCa-mSlo+hβ1 channels. It may be a novel regulator of blood pressure and provides a new therapeutic target for the treatment of hypertension. The HBD2 blockade of the BKCa channels may represent a new type of cross-talk between immune and cardiovascular systems.
人 β-防御素 2（HBD2）是一种富含半胱氨酸的阳离子抗菌肽，因其在先天免疫系统中的重要作用而闻名。大量研究表明其具有体外抗菌和趋化活性。在这项研究中，ELISA 分析表明，高血压患者血清中的 HBD2 显著下调。它通过作用于主要调节途径来松弛血管平滑肌，有助于血管平滑肌收缩。电生理学分析表明，HBD2 作为大电导钙激活钾（BKCa）-mSlo+hβ1 通道的开放剂，增加 BKCa 电流。突变分析表明，HBD2 通过与β1 环的 Leu41 和 Gln43 相互作用激活 BKCa-mSlo+hβ1 通道。体内实验表明，生理浓度的 4×至 6×HBD2 可显著降低猴子的血压，而 BKCa 通道的选择性阻滞剂 Paxilline 则抑制了这种作用。HBD2 是 BKCa-mSlo+hβ1 通道的第一个肽类开放剂。它可能是血压的新调节剂，为高血压的治疗提供了新的治疗靶点。HBD2 对 BKCa 通道的阻断可能代表免疫和心血管系统之间的一种新型串扰。
