磷脂酶 C-β3 对于血管收缩是不可或缺的,但对于血管增生却是不可或缺的。

IF 9.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Experimental and Molecular Medicine Pub Date : 2024-07-01 DOI:10.1038/s12276-024-01271-6
Seo Yeon Jin, Jung Min Ha, Hye Jin Kum, Ji Soo Ma, Hong Koo Ha, Sang Heon Song, Yong Ryoul Yang, Ho Lee, Yoon Soo Bae, Masahiro Yamamoto, Pann-Ghill Suh, Sun Sik Bae
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引用次数: 0

摘要

血管紧张素 II(AngII)可诱导血管平滑肌细胞(VSMC)收缩和增殖。血管紧张素 II 会激活磷脂酶 C-β(PLC-β),从而诱导 Ca2+ 迁移并产生活性氧(ROS)。由于收缩是收缩性血管内皮细胞的独特特性,与血管内皮细胞增殖相关的信号级联可能有所不同。然而,控制 VSMC 收缩或增殖的具体分子机制仍不清楚。抑制 PLC-β3、三磷酸肌醇(IP3)受体和 NOX 或沉默 PLC-β3 或 NOX1 均可抑制 AngII 诱导的 ROS 生成、迁移和增殖,但 NOX4 却不能抑制。然而,药物抑制或沉默 PLC-β3 或 NOX 并不影响 AngII 诱导的 VSMC 收缩。此外,从 PLC-β3∆SMC、NOX1-/-、NOX4-/- 和正常对照小鼠分离的肠系膜动脉受 AngII 依赖性收缩的情况相似。抑制 L 型钙通道罗-相关激酶 2(ROCK2)或肌球蛋白轻链激酶(MLCK)可阻断 AngII 诱导的 VSMC 收缩和肠系膜动脉收缩。在 PLC-β3∆SMC 小鼠中,ROCK2 和 MLCK 的活化被显著诱导,而细胞外培养基中 Ca2+ 的耗竭抑制了 AngII 诱导的 ROCK2、MLCK 活化和血管收缩。NOX1-/-和 PLC-β3∆SMC 小鼠明显诱发了 AngII 诱导的高血压,而 NOX1-/- 和 PLC-β3∆SMC 小鼠则明显抑制了 LCCA 结扎诱导的新内膜形成。这些结果表明,PLC-β3 通过 NOX1 介导的 ROS 生成对血管增生是必不可少的,但对血管收缩或血压调节则是非必需的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Phospholipase C-β3 is dispensable for vascular constriction but indispensable for vascular hyperplasia
Angiotensin II (AngII) induces the contraction and proliferation of vascular smooth muscle cells (VSMCs). AngII activates phospholipase C-β (PLC-β), thereby inducing Ca2+ mobilization as well as the production of reactive oxygen species (ROS). Since contraction is a unique property of contractile VSMCs, signaling cascades related to the proliferation of VSMCs may differ. However, the specific molecular mechanism that controls the contraction or proliferation of VSMCs remains unclear. AngII-induced ROS production, migration, and proliferation were suppressed by inhibiting PLC-β3, inositol trisphosphate (IP3) receptor, and NOX or by silencing PLC-β3 or NOX1 but not by NOX4. However, pharmacological inhibition or silencing of PLC-β3 or NOX did not affect AngII-induced VSMC contraction. Furthermore, the AngII-dependent constriction of mesenteric arteries isolated from PLC-β3∆SMC, NOX1−/−, NOX4−/− and normal control mice was similar. AngII-induced VSMC contraction and mesenteric artery constriction were blocked by inhibiting the L-type calcium channel Rho-associated kinase 2 (ROCK2) or myosin light chain kinase (MLCK). The activation of ROCK2 and MLCK was significantly induced in PLC-β3∆SMC mice, whereas the depletion of Ca2+ in the extracellular medium suppressed the AngII-induced activation of ROCK2, MLCK, and vasoconstriction. AngII-induced hypertension was significantly induced in NOX1−/− and PLC-β3∆SMC mice, whereas LCCA ligation-induced neointima formation was significantly suppressed in NOX1−/− and PLC-β3∆SMC mice. These results suggest that PLC-β3 is essential for vascular hyperplasia through NOX1-mediated ROS production but is nonessential for vascular constriction or blood pressure regulation. Angiotensin II is important in heart health. It makes blood vessels tighten and grow. This study looked at how AngII affects the creation of reactive oxygen species (ROS, molecules that change cell function) in vascular smooth muscle cells (VSMCs, cells in blood vessel walls). The researchers tested how stopping certain cell signals changes ROS creation and cell behaviors like growth and movement. They found that a specific protein, PLC-β3, and an enzyme, NOX1, are key in this process. Stopping these molecules could lower ROS levels and change cell growth and movement, important for blood vessel health. Interestingly, these molecules didn’t affect blood vessel tightening, also controlled by AngII. This study could help develop new treatments for blood vessel diseases, potentially helping manage conditions like high blood pressure and heart disease. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
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来源期刊
Experimental and Molecular Medicine
Experimental and Molecular Medicine 医学-生化与分子生物学
CiteScore
19.50
自引率
0.80%
发文量
166
审稿时长
3 months
期刊介绍: Experimental & Molecular Medicine (EMM) stands as Korea's pioneering biochemistry journal, established in 1964 and rejuvenated in 1996 as an Open Access, fully peer-reviewed international journal. Dedicated to advancing translational research and showcasing recent breakthroughs in the biomedical realm, EMM invites submissions encompassing genetic, molecular, and cellular studies of human physiology and diseases. Emphasizing the correlation between experimental and translational research and enhanced clinical benefits, the journal actively encourages contributions employing specific molecular tools. Welcoming studies that bridge basic discoveries with clinical relevance, alongside articles demonstrating clear in vivo significance and novelty, Experimental & Molecular Medicine proudly serves as an open-access, online-only repository of cutting-edge medical research.
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