成春锋,方红城

液液相分离（Liquid-Liquid Phase Separation, LLPS）作为近年来生物物理学领域的重要发现，其与心血管疾病（CVD）的关联逐渐成为研究热点。本文结合最新研究进展，系统阐述LLPS在心血管疾病中的分子机制、病理作用及潜在治疗价值。

相分离；心力衰竭；心脏纤维化；心肌缺血再灌注损伤；动脉粥样硬化

[1] WHEELER J R, MATHENY T, JAIN S, et al. Distinct stages in stress granule assembly and disassembly[J]. Elife, 2016, 5 [2] XIE S, CHEN M, FANG W, et al. Diminished arachidonate 5-lipoxygenase perturbs phase separation and transcriptional response of Runx2 to reverse pathological ventricular remodeling[J]. EBioMedicine, 2022, 86: 104359. [3] YIN Q, LU H, BAI Y, et al. A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway[J]. Br J Pharmacol, 2015, 172(23): 5573-5585. [4] JIANG Y, GU J, NIU X, et al. Phosphorylation-Regulated Dynamic Phase Separation of HIP-55 Protects Against Heart Failure[J]. Circulation, 2024, 150(12): 938-951. [5] CHEN J, HUANG Q, LI J, et al. Panax ginseng against myocardial ischemia/reperfusion injury: A review of preclinical evidence and potential mechanisms[J]. J Ethnopharmacol, 2023, 300: 115715. [6] CHEN L, MAO L S, XUE J Y, et al. Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome[J]. Life Sci, 2024, 355: 122998. [7] SHEN S, WANG Z, SUN H, et al. Role of NLRP3 Inflammasome in Myocardial Ischemia-Reperfusion Injury and Ventricular Remodeling[J]. Med Sci Monit, 2022, 28: e934255. [8] YU B, MA J, LI J, et al. Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics[J]. Nat Commun, 2020, 11(1): 2549. [9] MORIWAKI K, FARIAS LUZ N, BALAJI S, et al. The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages[J]. J Immunol, 2016, 196(1): 407-415. [10] LIU S, BI Y, HAN T, et al. The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis[J]. Cell Discov, 2024, 10(1): 24. [11] WANG X, SHEN Y, SHANG M, et al. Endothelial mechanobiology in atherosclerosis[J]. Cardiovasc Res, 2023, 119(8): 1656-1675. [12] LIM X R, HARRAZ O F. Mechanosensing by Vascular Endothelium[J]. Annu Rev Physiol, 2024, 86: 71-97. [13] PLUSKOTA E, BLEDZKA K M, BIALKOWSKA K, et al. Kindlin-2 interacts with endothelial adherens junctions to support vascular barrier integrity[J]. J Physiol, 2017, 595(20): 6443-6462. [14] MA N, WU F, LIU J, et al. Kindlin-2 Phase Separation in Response to Flow Controls Vascular Stability[J]. Circ Res, 2024, 135(12): 1141-1160. [15] PAKSHIR P, NOSKOVICOVA N, LODYGA M, et al. The myofibroblast at a glance[J]. J Cell Sci, 2020, 133(13) [16] BERRY M F, ENGLER A J, WOO Y J, et al. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance[J]. Am J Physiol Heart Circ Physiol, 2006, 290(6): H2196-2203. [17] FIGEAC N, MOHAMED A D, SUN C, et al. VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle[J]. J Cell Sci, 2019, 132(13) [18] HORII Y, MATSUDA S, TOYOTA C, et al. VGLL3 is a mechanosensitive protein that promotes cardiac fibrosis through liquid-liquid phase separation[J]. Nat Commun, 2023, 14(1): 550. [19] CHENG X, CASE L B. Phase separation in chemical and mechanical signal transduction[J]. Curr Opin Cell Biol, 2023, 85: 102243.

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