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LIM激酶在心血管健康与疾病中的作用

LIM kinases in cardiovascular health and disease.

作者信息

Lateef Olubodun M, Foote Christopher, Power Gavin, Manrique-Acevedo Camila, Padilla Jaume, Martinez-Lemus Luis A

机构信息

NextGen Precision Health, University of Missouri, Columbia, MO, United States.

Department of Medical Pharmacology and Physiology, University of Missouri Columbia, Columbia, MO, United States.

出版信息

Front Physiol. 2024 Dec 18;15:1506356. doi: 10.3389/fphys.2024.1506356. eCollection 2024.


DOI:10.3389/fphys.2024.1506356
PMID:39744707
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11688343/
Abstract

The Lim Kinase (LIMK) family of serine/threonine kinases is comprised of LIMK1 and LIMK2, which are central regulators of cytoskeletal dynamics via their well-characterized roles in promoting actin polymerization and destabilizing the cellular microtubular network. The LIMKs have been demonstrated to modulate several fundamental physiological processes, including cell cycle progression, cell motility and migration, and cell differentiation. These processes play important roles in maintaining cardiovascular health. However, LIMK activity in healthy and pathological states of the cardiovascular system is poorly characterized. This review highlights the cellular and molecular mechanisms involved in LIMK activation and inactivation, examining its roles in the pathophysiology of vascular and cardiac diseases such as hypertension, aneurysm, atrial fibrillation, and valvular heart disease. It addresses the LIMKs' involvement in processes that support cardiovascular health, including vasculogenesis, angiogenesis, and endothelial mechanotransduction. The review also features how LIMK activity participates in endothelial cell, vascular smooth muscle cell, and cardiomyocyte physiology and its implications in pathological states. A few recent preclinical studies demonstrate the therapeutic potential of LIMK inhibition. We conclude by proposing that future research should focus on the potential clinical relevance of LIMK inhibitors as therapeutic agents to reduce the burden of cardiovascular disease and improve patient outcomes.

摘要

丝氨酸/苏氨酸激酶的LIM激酶(LIMK)家族由LIMK1和LIMK2组成,它们通过在促进肌动蛋白聚合和破坏细胞微管网络方面的明确作用,成为细胞骨架动力学的核心调节因子。LIMK已被证明可调节多种基本生理过程,包括细胞周期进程、细胞运动和迁移以及细胞分化。这些过程在维持心血管健康中发挥着重要作用。然而,LIMK在心血管系统健康和病理状态下的活性特征尚不明确。本综述重点介绍了LIMK激活和失活所涉及的细胞和分子机制,探讨了其在高血压、动脉瘤、心房颤动和心脏瓣膜病等血管和心脏疾病病理生理学中的作用。它阐述了LIMK参与支持心血管健康的过程,包括血管生成、血管发生和内皮机械转导。该综述还介绍了LIMK活性如何参与内皮细胞、血管平滑肌细胞和心肌细胞的生理学及其在病理状态中的影响。最近的一些临床前研究证明了抑制LIMK的治疗潜力。我们在结论中提出,未来的研究应关注LIMK抑制剂作为治疗药物的潜在临床相关性,以减轻心血管疾病负担并改善患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/247e47cc3035/fphys-15-1506356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/5e48d42543f5/FPHYS_fphys-2024-1506356_wc_abs.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/a2c98c0d8926/fphys-15-1506356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/082ae3dfa18c/fphys-15-1506356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/48ac9ace1d88/fphys-15-1506356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/247e47cc3035/fphys-15-1506356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/5e48d42543f5/FPHYS_fphys-2024-1506356_wc_abs.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/a2c98c0d8926/fphys-15-1506356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/082ae3dfa18c/fphys-15-1506356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/48ac9ace1d88/fphys-15-1506356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd10/11688343/247e47cc3035/fphys-15-1506356-g004.jpg

相似文献

[1]
LIM kinases in cardiovascular health and disease.

Front Physiol. 2024-12-18

[2]
LIMK (LIM Kinase) Inhibition Prevents Vasoconstriction- and Hypertension-Induced Arterial Stiffening and Remodeling.

Hypertension. 2020-8

[3]
LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.

Cells. 2023-3-4

[4]
Lim kinases, regulators of actin dynamics.

Int J Biochem Cell Biol. 2007

[5]
LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators.

Med Res Rev. 2011-1-16

[6]
LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells.

Zebrafish. 2009-12

[7]
Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle.

Acta Pharm Sin B. 2021-7

[8]
LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2.

Oncogene. 2013-8-12

[9]
Tetrahydropyridine LIMK inhibitors: Structure activity studies and biological characterization.

Eur J Med Chem. 2024-5-5

[10]
Computational Development of Allosteric Peptide Inhibitors Targeting LIM Kinases as a Novel Therapeutic Intervention.

Cell Biochem Biophys. 2025-3-18

本文引用的文献

[1]
Reduced cofilin activity as a mechanism contributing to endothelial cell stiffening in type 2 diabetes.

Am J Physiol Heart Circ Physiol. 2025-1-1

[2]
Regulation and signaling of the LIM domain kinases.

Bioessays. 2025-1

[3]
Integrating molecular and cellular components of endothelial shear stress mechanotransduction.

Am J Physiol Heart Circ Physiol. 2024-10-1

[4]
Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.

Commun Biol. 2024-7-30

[5]
Tetrahydropyridine LIMK inhibitors: Structure activity studies and biological characterization.

Eur J Med Chem. 2024-5-5

[6]
DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy.

Research (Wash D C). 2024-3-26

[7]
Investigating LIM (Lin-11, Isl-1, and Mec-3) Kinases and Their Correlation with Pathological Events and Microtubule Dynamics in an Experimental Model of Spinal Cord Injury in Rats.

ACS Pharmacol Transl Sci. 2024-2-7

[8]
Autoregulation of the LIM kinases by their PDZ domain.

Nat Commun. 2023-12-19

[9]
PDZ and LIM Domain-Encoding Genes: Their Role in Cancer Development.

Cancers (Basel). 2023-10-19

[10]
The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix-Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids.

Cells. 2023-8-9

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