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진서연Seo Yeon Jin

부산대학교 의과대학

Exp. Mol. Med., Jul 01 2024, | https://doi.org/10.1038/s12276-024-01271-6 Phospholipase C-β3 is dispensable for vascular constriction but indispensable for vascular hyperplasia

Seo Yeon Jin¹, Jung Min Ha¹, Hye Jin Kum¹, Ji Soo Ma², Hong Koo Ha³, Sang Heon Song⁴, Yong Ryoul Yang⁵, Ho Lee⁶, Yoon Soo Bae⁷, Masahiro Yamamoto², Pann-Ghill Suh⁸ and Sun Sik Bae¹

¹Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.

²Department of Immunoparasitology, Osaka University, Suita, Japan.

³Department of Urology, Pusan National University Hospital, Busan, Republic of Korea.

⁴Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea.

⁵Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.

⁶Carcinogenesis and Metastasis Research Branch, National Cancer Center, Goyang, Republic of Korea.

⁷Department of Life Science, Ewha Womans University, Seoul, Republic of Korea.

⁸Korea Brain Research Institute, Daegu, Republic of Korea.

Corresponding author

Correspondence to Sun Sik Bae.

Abstract

Angiotensin II (AngII) induces the contraction and proliferation of vascular smooth muscle cells (VSMCs). AngII activates phospholipase C-β (PLC-β), thereby inducing Ca ²⁺ 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 (IP ₃) 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 Ca ²⁺ 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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-02)
연구진국내 연구진
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