Ferreira Gonzalo, Cardozo Romina, Chavarria Luisina, Santander Axel, Sobrevia Luis, Chang Wakam, Gundersen Gregg, Nicolson Garth L
Department of Biophysics, Faculty of Medicine, Universidad de La República, Montevideo, Uruguay.
Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Physiol. 2025 Feb 3. doi: 10.1113/JP285906.
The LINC (linker of nucleoskeleton and cytoskeleton) complex is a critical component of the cellular architecture that bridges the nucleoskeleton and cytoskeleton and mediates mechanotransduction to and from the nucleus. Though it plays important roles in all blood vessels, it is in arterioles that this complex plays a pivotal role in maintaining endothelial cell integrity, regulating vascular tone, forming new microvessels and modulating responses to mechanical and biochemical stimuli. It is also important in vascular smooth muscle cells and fibroblasts, where it possibly plays a role in the contractile to secretory phenotypic transformation during atherosclerosis and vascular ageing, and in fibroblasts' migration and inflammatory responses in the adventitia. Physiologically, the LINC complex contributes to the stability of arteriolar structure, adaptations to changes in blood flow and injury repair mechanisms. Pathologically, dysregulation or mutations in LINC complex components can lead to compromised endothelial function, vascular remodelling and exacerbation of cardiovascular diseases such as atherosclerosis (arteriolosclerosis). This review summarizes our current understanding of the roles of the LINC complex in cells from arterioles, highlighting its most important physiological functions, exploring its implications for vascular pathology and emphasizing some of its functional characteristics in endothelial cells. By elucidating the LINC complex's role in health and disease, we aim to provide insights that could improve future therapeutic strategies targeting LINC complex-related vascular disorders.
LINC（核骨架与细胞骨架连接物）复合体是细胞结构的关键组成部分，它连接核骨架和细胞骨架，并介导细胞核与外界之间的机械转导。尽管它在所有血管中都发挥着重要作用，但在小动脉中，该复合体在维持内皮细胞完整性、调节血管张力、形成新的微血管以及调节对机械和生化刺激的反应方面起着关键作用。它在血管平滑肌细胞和成纤维细胞中也很重要，在动脉粥样硬化和血管衰老过程中，它可能在收缩型到分泌型的表型转变中发挥作用，并且在成纤维细胞在外膜中的迁移和炎症反应中也发挥作用。在生理上，LINC复合体有助于小动脉结构的稳定性、对血流变化的适应以及损伤修复机制。在病理上，LINC复合体成分的失调或突变可导致内皮功能受损、血管重塑以及心血管疾病如动脉粥样硬化（小动脉硬化）的加剧。本综述总结了我们目前对LINC复合体在小动脉细胞中作用的理解，突出了其最重要的生理功能，探讨了其对血管病理学的影响，并强调了其在内皮细胞中的一些功能特征。通过阐明LINC复合体在健康和疾病中的作用，我们旨在提供一些见解，以改进未来针对与LINC复合体相关的血管疾病的治疗策略。
