REFERENCES
1. González A, López B, Ravassa S, et al. Myocardial interstitial fibrosis in hypertensive heart disease: from mechanisms to clinical management. Hypertension. 2024;81:218-28.
2. Zhang Q, He Y, Li Y, et al. Matricellular protein Cilp1 promotes myocardial fibrosis in response to myocardial infarction. Circ Res. 2021;129:1021-35.
3. Eijgenraam TR, Silljé HH, De Boer RA. Current understanding of fibrosis in genetic cardiomyopathies. Trends Cardiovasc Med. 2020;30:353-61.
4. Liu K, Zheng L, Huang Q, et al. Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury. Chin Med. 2025;20:90.
5. Li L, Zhao Q, Kong W. Extracellular matrix remodeling and cardiac fibrosis. Matrix Biol. 2018;68-9:490-506.
6. Sutherland TE, Dyer DP, Allen JE. The extracellular matrix and the immune system: a mutually dependent relationship. Science. 2023;379:eabp8964.
7. Pathak A, Kumar S. Independent regulation of tumor cell migration by matrix stiffness and confinement. Proc Natl Acad Sci USA. 2012;109:10334-9.
8. Wang T, Abolghasemzade S, Mckee BP, et al. Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization. Nat Commun. 2024;15:10151.
9. Holt M, Lin J, Cicka M, Wong A, Epelman S, Lavine KJ. Dissecting and visualizing the functional diversity of cardiac macrophages. Circ Res. 2024;134:1791-807.
10. Wang J, Wang J, Zhang Y, et al. Identifying vascular stiffening-sensitive macrophages through integration of single-cell transcriptomics and imaging flow cytometry. Biophys Rep. 2025;11:393.
11. Khalsa P, Ge W, Zia Uddin M, Hadjiargyrou M. Integrin α2β1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin. Neuroscience. 2004;129:447-59.
12. Ingber DE. Mechanosensation through integrins: cells act locally but think globally. Proc Natl Acad Sci USA. 2003;100:1472-4.
13. Liu J, Wang X, He F, Chen X, Yi X. Mechanosensitive calcium ion channels Piezo1: a therapeutic target in liver disease. Mol Ther Nucl Acids. 2025;36:102695.
14. Zhang X, Hou L, Li F, et al. Piezo1-mediated mechanosensation in bone marrow macrophages promotes vascular niche regeneration after irradiation injury. Theranostics. 2022;12:1621-38.
15. Meli VS, Veerasubramanian PK, Downing TL, Wang W, Liu WF. Mechanosensation to inflammation: roles for YAP/TAZ in innate immune cells. Sci Signal. 2023;16:eadc9656.
16. Panciera T, Azzolin L, Cordenonsi M, Piccolo S. Mechanobiology of YAP and TAZ in physiology and disease. Nat Rev Mol Cell Biol. 2017;18:758-70.
17. Souilhol C, Tardajos Ayllon B, Li X, et al. JAG1-NOTCH4 mechanosensing drives atherosclerosis. Sci Adv. 2022;8:eabo7958.
18. Foldi J, Chung AY, Xu H, et al. Autoamplification of notch signaling in macrophages by TLR-induced and RBP-J-dependent induction of Jagged1. J Immunol. 2010;185:5023-31.
19. Ghazal R, Wang M, Liu D, Tschumperlin DJ, Pereira NL. Cardiac fibrosis in the multi-omics era: implications for heart failure. Circ Res. 2025;136:773-802.
20. Frangogiannis NG. The extracellular matrix in ischemic and nonischemic heart failure. Circ Res. 2019;125:117-46.
21. Cieslik KA, Taffet GE, Carlson S, Hermosillo J, Trial J, Entman ML. Immune-inflammatory dysregulation modulates the incidence of progressive fibrosis and diastolic stiffness in the aging heart. J Mol Cell Cardiol. 2011;50:248-56.
22. Esfahani NS, Wu Q, Kumar N, Ganesan LP, Lafuse WP, Rajaram MVS. Aging influences the cardiac macrophage phenotype and function during steady state and during inflammation. Aging Cell. 2021;20:e13438.
23. Yu K, Yuan W, Wang H, Li Y. Extracellular matrix stiffness and tumor-associated macrophage polarization: new fields affecting immune exclusion. Cancer Immunol Immunother. 2024;73:115.
24. Meli VS, Rowley AT, Veerasubramanian PK, Heedy SE, Liu WF, Wang S. Modulation of stiffness-dependent macrophage inflammatory responses by collagen deposition. ACS Biomater Sci Eng. 2024;10:2212-23.
25. Wang Y, Shi R, Zhai R, et al. Matrix stiffness regulates macrophage polarization in atherosclerosis. Pharmacol Res. 2022;179:106236.
26. Liu H, Fan P, Jin F, Huang G, Guo X, Xu F. Dynamic and static biomechanical traits of cardiac fibrosis. Front Bioeng Biotechnol. 2022;10:1042030.
27. Curtis MW, Russell B. Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling. Pflugers Arch Eur J Physiol. 2011;462:105-17.
28. Happe CL, Engler AJ. Mechanical forces reshape differentiation cues that guide cardiomyogenesis. Circ Res. 2016;118:296-310.
29. Balachandran K, Alford PW, Wylie-Sears J, et al. Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve. Proc Natl Acad Sci USA. 2011;108:19943-8.
30. Samady H, Eshtehardi P, Mcdaniel MC, et al. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation. 2011;124:779-88.
31. Cho S, Rhee S, Madl CM, et al. Selective inhibition of stromal mechanosensing suppresses cardiac fibrosis. Nature. 2025;642:766-75.
32. Omar AMS, Bansal M, Sengupta PP. Advances in echocardiographic imaging in heart failure with reduced and preserved ejection fraction. Circ Res. 2016;119:357-74.
33. Petrescu A, Cvijic M, Wouters L, et al. Ultrasound shear wave elastography for detection of myocardial fibrosis. Eur Heart J. 2025;26:1537-45.
34. Villemain O, Correia M, Mousseaux E, et al. Myocardial stiffness evaluation using noninvasive shear wave imaging in healthy and hypertrophic cardiomyopathic adults. JACC Cardiovasc Imaging. 2019;12:1135-45.
35. Miao L, Lu Y, Nusrat A, et al. β1 integrins regulate cellular behaviour and cardiomyocyte organization during ventricular wall formation. Cardiovasc Res. 2024;120:1279-94.
36. Prakash A, Smith PO, Iskratsch T. Role of the extracellular matrix in cardiac ageing. Nat Mater. 2025;24:1337-9.
37. Cleutjens JP, Creemers EE. Integration of concepts: cardiac extracellular matrix remodeling after myocardial infarction. J Card Fail. 2002;8:S344-8.
38. Weil BR, Neelamegham S. Selectins and immune cells in acute myocardial infarction and post-infarction ventricular remodeling: pathophysiology and novel treatments. Front Immunol. 2019;10:300.
39. Ibrahim AM, Elfawy HA, Terracciano CM, Yacoub M. Matrisome remodeling in the myocardium of hypertrophic cardiomyopathy; novel targets for molecular diagnostics. Front Cell Dev Biol. 2025;13:1641584.
40. Buck KM, Rogers HT, Gregorich ZR, et al. Extracellular matrix alterations in chronic ischemic cardiomyopathy revealed by quantitative proteomics. JCI Insight. 2025;10:e196933.
41. Wittig C, Szulcek R. Extracellular matrix protein ratios in the human heart and vessels: how to distinguish pathological from physiological changes? Front Physiol. 2021;12:708656.
42. Wei S, Chow LT, Shum IO, Qin L, Sanderson JE. Left and right ventricular collagen type I/III ratios and remodeling post-myocardial infarction. J Card Fail. 1999;5:117-26.
43. Sridhar KC, Mehl J, Klingel K, et al. Loss of fibronectin fiber tension is inherent to ECM remodeling in human myocarditis and post-inflammatory fibrosis. Matrix Biology Plus. 2025;28:100182.
44. Sottile J, Hocking DC. Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions. Mol Biol Cell. 2002;13:3546-59.
45. Liu P, Sun M, Sader S. Matrix metalloproteinases in cardiovascular disease. Can J Cardiol. 2006;22:25B-30B.
46. Klein T, Bischoff R. Physiology and pathophysiology of matrix metalloproteases. Amino Acids. 2010;41:271-90.
47. Garvin P, Nilsson L, Carstensen J, Jonasson L, Kristenson M. Circulating matrix metalloproteinase-9 is associated with cardiovascular risk factors in a middle-aged normal population. PLoS ONE. 2008;3:e1774.
48. Toba H, Cannon PL, Yabluchanskiy A, Iyer RP, D’armiento J, Lindsey ML. Transgenic overexpression of macrophage matrix metalloproteinase-9 exacerbates age-related cardiac hypertrophy, vessel rarefaction, inflammation, and fibrosis. Am J Physiol Heart Circ Physiol. 2017;312:H375-83.
49. Voorhees AP, Deleon-pennell KY, Ma Y, et al. Building a better infarct: modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction. J Mol Cell Cardiol. 2015;85:229-39.
50. Kitano T, Sasaki T, Matsui T, et al. Transcriptome analysis identified SPP1‐positive monocytes as a key in extracellular matrix formation in thrombi. J Am Heart Assoc. 2025;14:e044299.
51. Du X, Liu T, Shen C, et al. RETRACTED ARTICLE: anti-fibrotic mechanism of SPP1 knockdown in atrial fibrosis associates with inhibited mitochondrial DNA damage and TGF-β/SREBP2/PCSK9 signaling. Cell Death Discov. 2022;8:246.
52. Hoeft K, Schaefer GJ, Kim H, et al. Platelet-instructed SPP1+ macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner. Cell Rep. 2023;42:112131.
53. Lee J, Wang M, Sudhir P, Chen G, Chi C, Chen J. Osteopontin promotes integrin activation through outside-in and inside-out mechanisms: OPN-CD44V interaction enhances survival in gastrointestinal cancer cells. Cancer Res. 2007;67:2089-97.
54. Weber GF, Ashkar S, Glimcher MJ, Cantor H. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science. 1996;271:509-12.
55. Zhang J, Song J, Tang S, et al. Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation. Cell Rep. 2023;42:112620.
56. Ghasemi H, Mousavibahar SH, Hashemnia M, Karimi J, Khodadadi I, Tavilani H. Transitional cell carcinoma matrix stiffness regulates the osteopontin and YAP expression in recurrent patients. Mol Biol Rep. 2021;48:4253-62.
57. Lok ZSY, Lyle AN. Osteopontin in vascular disease: friend or Foe? Arterioscler Thromb Vasc Biol. 2019;39:613-22.
58. Speer MY, Mckee MD, Guldberg RE, et al. Inactivation of the osteopontin gene enhances vascular calcification of matrix gla protein-deficient mice. J Exp Med. 2002;196:1047-55.
59. Mabatha KC, Letuka P, Aremu O, Zulu MZ. Macrophages of the heart: homeostasis and disease. Biomed J. 2026;49:100867.
60. Chen R, Zhang H, Tang B, et al. Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets. Sig Transduct Target Ther. 2024;9:130.
61. Yap J, Irei J, Lozano-gerona J, Vanapruks S, Bishop T, Boisvert WA. Macrophages in cardiac remodelling after myocardial infarction. Nat Rev Cardiol. 2023;20:373-85.
62. Querceto S, Santoro R, Gowran A, et al. The harder the climb the better the view: the impact of substrate stiffness on cardiomyocyte fate. J Mol Cell Cardiol. 2022;166:36-49.
63. Park I, Marquardt RR. Effects of niacin deficiency on pyridine nucleotide levels and enzyme activities in various organs of young growing quail. J Nut. 1982;112:863-73.
64. Xu Z, Yu J, Chen D, et al. Extracellular matrix stiffness regulates the proliferation and migration capacities of lymphatic endothelial cells via FAT1. Front Cell Dev Biol. 2025;13:1667154.
65. Li M, Wu J, Hu G, et al. Pathological matrix stiffness promotes cardiac fibroblast differentiation through the POU2F1 signaling pathway. Sci China Life Sci. 2020;64:242-54.
66. Felisbino MB, Rubino M, Travers JG, et al. Substrate stiffness modulates cardiac fibroblast activation, senescence and proinflammatory secretory phenotype. Am J Physiol Heart Circ Physiol. 2023;326:H61-73.
67. Yang S, Penna V, Lavine KJ. Functional diversity of cardiac macrophages in health and disease. Nat Rev Cardiol. 2025;22:431-42.
68. Jin J, Wang Y, Liu Y, Chakrabarti S, Su Z. Cardiac resident macrophages: spatiotemporal distribution, development, physiological functions, and their translational potential on cardiac diseases. Acta Pharm Sin B. 2024;14:1483-93.
69. Zhang Y, Wu Y, Li M, Mijiti A, Cheng L. Identification of macrophage driver genes in fibrosis caused by different heart diseases based on omics integration. J Transl Med. 2024;22:839.
70. Li S, Ge T, Xu X, et al. Integrating scRNA-seq to explore novel macrophage infiltration-associated biomarkers for diagnosis of heart failure. BMC Cardiovasc Disord. 2023;23:560.
71. Uhlig M, Billig S, Wienhold J, Schumacher D. Pro-fibrotic macrophage subtypes: SPP1+ Macrophages as a key player and therapeutic target in cardiac fibrosis? Cells. 2025;14:345.
72. Li R, Hanna A, Huang S, et al. Macrophages in the infarcted heart acquire a fibrogenic phenotype, expressing matricellular proteins, but do not undergo fibroblast conversion. J Mol Cell Cardiol. 2024;196:152-67.
73. Ni Y, Qi H, Zhang F, et al. Macrophages modulate stiffness-related foreign body responses through plasma membrane deformation. Proc Natl Acad Sci USA. 2023;120:e2213837120.
74. Haschak M, Lopresti S, Stahl E, Dash S, Popovich B, Brown BN. Macrophage phenotype and function are dependent upon the composition and biomechanics of the local cardiac tissue microenvironment. Aging. 2021;13:16938-56.
75. Wang Y, Chaffee TS, Larue RS, et al. Tissue-resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice. eLife. 2020;9:e57438.
76. Simões FC, Cahill TJ, Kenyon A, et al. Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair. Nat Commun. 2020;11:600.
77. Su Y, Yin X. The Molecular mechanism of macrophages in response to mechanical stress. Ann Biomed Eng. 2024;53:318-30.
78. Yin Z, Wen T, Cao X, et al. The transcription factor RBPJ is required for inflammatory macrophage activation in thoracic aortic dissection by mediating mechanotransduction-induced glycolysis. Cell Mol Life Sci. 2025;82:370.
79. Tao D, Wang H, Chang S, et al. Matrix viscoelasticity orchestrates osteogenesis via mechanotransduction mediated metabolic switch in macrophages. Adv Healthc Mater. 2025;14:2405097.
80. Zhang S, Chen R, Chakrabarti S, Su Z. Resident macrophages as potential therapeutic targets for cardiac ageing and injury. Clin Trans Imm. 2020;9:e1167.
81. Lin PK, Davis GE. Extracellular matrix remodeling in vascular disease: defining its regulators and pathological influence. Arterioscler Thromb Vasc Biol. 2023;43:1599-616.
82. Xu Y, Ying L, Lang JK, Hinz B, Zhao R. Modeling mechanical activation of macrophages during pulmonary fibrogenesis for targeted anti-fibrosis therapy. Sci Adv. 2024;10:eadj9559.
83. Wang Y, Wang J, Zhang J, et al. Stiffness sensing via Piezo1 enhances macrophage efferocytosis and promotes the resolution of liver fibrosis. Sci Adv. 2024;10:eadj3289.
85. Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol. 2011;3:a004994.
87. Geiger B, Spatz JP, Bershadsky AD. Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol. 2009;10:21-33.
88. Park JE, Jebamercy G, Pazhanchamy K, et al. Aging-induced isoDGR-modified fibronectin activates monocytic and endothelial cells to promote atherosclerosis. Atherosclerosis. 2021;324:58-68.
89. Li R, Chen B, Kubota A, et al. Protective effects of macrophage-specific integrin α5 in myocardial infarction are associated with accentuated angiogenesis. Nat Commun. 2023;14:7555.
90. Chen C, Li R, Ross RS, Manso AM. Integrins and integrin-related proteins in cardiac fibrosis. J Mol Cell Cardiol. 2016;93:162-74.
91. Li R, Huang S, Hanna A, et al. Macrophage ITGAV is dispensable for post-infarction remodeling in mice and does not mediate fibronectin responses. Commun Biol. 2025;9:29.
92. Chen M, Zhang Y, Zhou P, et al. Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway. Bioact Mater. 2020;5:880-90.
93. Xing X, Wang Y, Zhang X, et al. Matrix stiffness‐mediated effects on macrophages polarization and their LOXL2 expression. FEBS J. 2020;288:3465-77.
94. Shimojo N, Hashizume R, Kanayama K, et al. Tenascin-C May accelerate cardiac fibrosis by activating macrophages via the integrin αVβ3/nuclear factor-κB/interleukin-6 axis. Hypertension. 2015;66:757-66.
95. Kim H, Nam J. The multifaceted role of YAP in the tumor microenvironment and its therapeutic implications in cancer. Exp Mol Med. 2025;57:2201-13.
96. Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179-83.
97. Feng H, Hu W, Liu Y, et al. Macrophages in ventricular remodeling and heart failure: orchestrators of inflammation and repair. Front Immunol. 2025;16:1682294.
98. Li R, Huang W. Yes-associated protein and transcriptional coactivator with PDZ-binding motif in cardiovascular diseases. Int J Mol Sci. 2023;24:1666.
99. Mani A, Hwa J, Martin KA. Sugar, fat, and YAP: a recipe for vascular stiffness. Circ Res. 2022;130:868-70.
100. Wang K, Yeh Y, Nguyen P, et al. Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis. Proc Natl Acad Sci USA. 2016;113:11525-30.
101. Azad T, Ghahremani M, Yang X. The role of YAP and TAZ in angiogenesis and vascular mimicry. Cells. 2019;8:407.
102. Sanchez-lozano M, Chirikian O, Lane KV, Dow LP, Castillo EA, Pruitt B. Stretch-activated nuclear YAP localization in cardiomyocytes. Biophys J. 2023;122:264a.
103. Wang Y, Zhang J, Wu B, et al. IL-37 improves mice myocardial infarction via inhibiting YAP-NLRP3 signaling mediated macrophage programming. Eur J Pharmacol. 2022;934:175293.
104. Li B, He J, Lv H, et al. c-Abl regulates YAPY357 phosphorylation to activate endothelial atherogenic responses to disturbed flow. J Clin Investig. 2019;129:1167-79.
105. Sugihara T, Werneburg NW, Hernandez MC, et al. YAP tyrosine phosphorylation and nuclear localization in cholangiocarcinoma cells are regulated by LCK and independent of LATS activity. Mol Cancer Res. 2018;16:1556-67.
106. Zhao B, Li L, Tumaneng K, Wang C, Guan K. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP. Genes Dev. 2010;24:72-85.
107. Liu M, Yan M, Lv H, et al. Macrophage K63-linked ubiquitination of YAP Promotes its nuclear localization and exacerbates atherosclerosis. Cell Rep. 2020;32:107990.
108. Mei F, Guo Y, Wang Y, et al. Matrix stiffness regulates macrophage polarisation via the Piezo1‐YAP signalling axis. Cell Prolif. 2024;57:e13640.
109. Lee J, Park JH, Lee JH, Lee H, Knowles JC, Kim H. Matrix-enabled mechanobiological modulation of osteoimmunology. Matter. 2022;5:3194-224.
110. Mia MM, Cibi DM, Abdul Ghani SAB, et al. YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction. PLoS Biol. 2020;18:e3000941.
111. Meli VS, Atcha H, Veerasubramanian PK, et al. YAP-mediated mechanotransduction tunes the macrophage inflammatory response. Sci Adv. 2020;6:eabb8471.
112. Zhao L, Guan H, Song C, et al. YAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism. Bone. 2018;110:177-86.
113. Xiao B. Mechanisms of mechanotransduction and physiological roles of PIEZO channels. Nat Rev Mol Cell Biol. 2024;25:886-903.
114. Pathak MM, Nourse JL, Tran T, et al. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc Natl Acad Sci USA. 2014;111:16148-53.
115. Lai A, Thurgood P, Cox CD, et al. Piezo1 response to shear stress is controlled by the components of the extracellular matrix. ACS Appl Mater Interfaces. 2022;14:40559-68.
116. Coste B, Delmas P. PIEZO ion channels in cardiovascular functions and diseases. Circ Res. 2024;134:572-91.
117. Chesler AT, Szczot M, Bharucha-Goebel D, et al. The role of PIEZO2 in human mechanosensation. N Engl J Med. 2016;375:1355-64.
118. Liu X, Niu W, Zhao S, Zhang W, Zhao Y, Li J. Piezo1: the potential new therapeutic target for fibrotic diseases. Prog Biophys Mol Biol. 2023;184:42-9.
119. Wen J, Guan Y, Niu H, Dang Y, Guan J. Targeting cardiac resident CCR2+ macrophage-secreted MCP-1 to attenuate inflammation after myocardial infarction. Acta Biomater. 2026;211:18-32.
120. Chen B, Frangogiannis NG. The role of macrophages in nonischemic heart failure. JACC: Basic Transl Sci. 2018;3:245-8.
121. Chen J, Zhu Z, Wang Y, Yu J, Zhang X, Xu Y. Cardiac resident macrophages in cardiovascular disease: from physiology to pathology. Heart. 2025;111:391-400.
122. He Y, Deng B, Liu S, et al. Myeloid Piezo1 deletion protects renal fibrosis by restraining macrophage infiltration and activation. Hypertension. 2022;79:918-31.
123. Atcha H, Kulkarni D, Meli VS, et al. Piezo1-mediated mechanotransduction enhances macrophage oxidized low-density lipoprotein uptake and atherogenesis. PNAS Nexus. 2024;3:pgae436.
124. Peng L, Xia Y, Zhao H, et al. Piezo1 upregulation in monocyte‐derived macrophages impairs post‐myocardial infarction cardiac repair via defective efferocytosis and enhanced ferroptosis. Adv Sci. 2025;13:e10991.
125. Zhang Y, Zhang Y, Song J, et al. Piezo1 knockdown activates PI3K/AKT and enhances SPP1 to drive M2 macrophage polarization and reduce cardiac inflammation. Sci Rep. 2026;16:4879.
126. Atcha H, Jairaman A, Holt JR, et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat Commun. 2021;12:3256.
127. Budde I, Ing D, Schwab A, Denes Petho Z. Mechanosensitive ion channels are essential for the durotaxis of pancreatic stellate cells. Biophys J. 2022;121:314a.
128. Espina JA, Marchant CL, Barriga EH. Durotaxis: the mechanical control of directed cell migration. FEBS J. 2021;289:2736-54.
129. Yang Y, Xie K, Jiang H. Durotaxis index of 3T3 fibroblast cells scales with stiff-to-soft membrane tension polarity. Biophys J. 2020;119:1427-38.
130. Mout R, Jing R, Tanaka-yano M, et al. Design of soluble Notch agonists that drive T cell development and boost immunity. Cell. 2025;188:5980-94.e28.
131. Rodriguez F, Sanlidag S, Sahlgren C. Mechanical regulation of the Notch signaling pathway. Curr Opin Cell Biol. 2023;85:102244.
132. Friedrich T, Ferrante F, Pioger L, et al. Notch-dependent and -independent functions of transcription factor RBPJ. Nucleic Acids Res. 2022;50:7925-37.
133. Min E, Schwartz MA. Translocating transcription factors in fluid shear stress-mediated vascular remodeling and disease. Exp Cell Res. 2019;376:92-7.
134. Karakaya C, Van Asten JGM, Ristori T, Sahlgren CM, Loerakker S. Mechano-regulated cell-cell signaling in the context of cardiovascular tissue engineering. Biomech Model Mechanobiol. 2021;21:5-54.
135. Li Z, Nie M, Yu L, et al. Blockade of the notch signaling pathway promotes M2 macrophage polarization to suppress cardiac fibrosis remodeling in mice with myocardial infarction. Front Cardiovasc Med. 2022;8:639476.
136. Pabois A, Pagie S, Gérard N, et al. Notch signaling mediates crosstalk between endothelial cells and macrophages via Dll4 and IL6 in cardiac microvascular inflammation. Biochem Pharmacol. 2016;104:95-107.
137. Bugeon L, Taylor HB, Progatzky F, et al. The NOTCH pathway contributes to cell fate decision in myelopoiesis. Haematologica. 2011;96:1753-60.
138. Cruz Tleugabulova M, Melo SP, Wong A, et al. Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade. Nat Commun. 2024;15:9575.
139. Yang Y, Ni M, Zong R, et al. Targeting Notch1-YAP circuit reprograms macrophage polarization and alleviates acute liver injury in mice. Cell Mol Gastroenterol Hepatol. 2023;15:1085-104.
140. Alonzo M, Kumar SA, Allen S, et al. Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation. Prog Biomater. 2020;9:125-37.
141. Cao Y, Lee BH, Peled HB, Venkatraman SS. Synthesis of stiffness‐tunable and cell‐responsive Gelatin-poly(ethylene glycol) hydrogel for three‐dimensional cell encapsulation. J Biomed Mater Res. 2016;104:2401-11.
142. Martinez-vidal L, Murdica V, Venegoni C, et al. Causal contributors to tissue stiffness and clinical relevance in urology. Commun Biol. 2021;4:1011.
143. Simon‐chica A, Klesen A, Emig R, et al. Piezo1 stretch‐activated channel activity differs between murine bone marrow‐derived and cardiac tissue‐resident macrophages. J Physiol. 2024;602:4437-56.
144. Herum KM, Choppe J, Kumar A, Engler AJ, Mcculloch AD. Mechanical regulation of cardiac fibroblast profibrotic phenotypes. Mol Biol Cell. 2017;28:1871-82.
145. Hiesinger W, Brukman MJ, Mccormick RC, et al. Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell-derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model. J Thorac Cardiov Sur. 2012;143:962-6.
146. Wang X, Senyo S. Microenvironment stiffness requires extracellular matrix proteins to modulate heart regeneration. FASEB J. 2021;35:03575.
147. Peña B, Adbel-hafiz M, Cavasin M, Mestroni L, Sbaizero O. Atomic force microscopy (AFM) applications in arrhythmogenic cardiomyopathy. Int J Mol Sci. 2022;23:3700.
148. Qiao Q, Sun Y, Wang J, et al. Independently tunable viscoelasticity in hydrogels as a mechanical cue for tissue engineering. Tissue Eng Part B Rev. 2026:19373341251377696.
149. Lai W, Geliang H, Bin X, Wang W. Effects of hydrogel stiffness and viscoelasticity on organoid culture: a comprehensive review. Mol Med. 2025;31:83.
150. O’hern C, Caywood S, Aminova S, et al. Human heart-macrophage assembloids mimic immune-cardiac interactions and enable arrhythmia disease modeling. Cell Stem Cell. 2025;32:1671-90.e13.
151. Walker JA, Beck GA, Campbell JH, Miller AD, Burdo TH, Williams KC. Anti‐α4 integrin antibody blocks monocyte/macrophage traffic to the heart and decreases cardiac pathology in a SIV infection model of AIDS. J Am Heart Assoc. 2015;4:e001932.
152. Craiu D, Dica AD, Pomeran C, Pescaru G, Menascu S, Simu M. Disease-modifying treatment options in very early onset multiple sclerosis—what choices are there for onset under 5 years of age? A systematic review. J Clin Med. 2025;14:8133.
153. Bledzka K, Smyth SS, Plow EF. Integrin αIIbβ3: from discovery to efficacious therapeutic target. Circ Res. 2013;112:1189-200.
154. Pugashetti R, Koo J. Efalizumab discontinuation: a practical strategy. J Dermatolog Treat. 2009;20:132-6.
155. Gordon KB, Papp KA, Hamilton TK, et al. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA. 2003;290:3073.
156. Bouri S, Johnston E. Vedolizumab: what is the benefit from increasing the dose frequency? Drug Ther Bull. 2022;60:183-7.
157. Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease. Ophthalmology. 2017;124:53-60.
158. Matsuoka K, Watanabe M, Ohmori T, et al. AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Gastroenterol Hepatol. 2022;7:648-57.
159. Weinreb PH, Simon KJ, Rayhorn P, et al. Function-blocking integrin αvβ6 monoclonal antibodies. J Biol Chem. 2004;279:17875-87.
160. Raghu G, Mouded M, Prasse A, et al. Randomized phase IIa clinical study of an anti-αvβ6 monoclonal antibody in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2022;206:1166-8.
161. Wang C, Zhu X, Feng W, et al. Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm. Am J Cancer Res. 2016;6:27-37.
162. Huang H, Wang T, Rousseau J, et al. Biomimetic nanodrug targets inflammation and suppresses YAP/TAZ to ameliorate atherosclerosis. Biomaterials. 2024;306:122505.
163. Masuyama M, Shimoda M, Seto I, et al. Targeting focal adhesion kinase inhibits cell migration and non-angiogenic vascularization in malignant breast cancer. Breast Cancer. 2025;33:188-99.
164. Hanna GJ, Stathis A, Lopez-Miranda E, et al. A phase I study of the pan-notch inhibitor CB-103 for patients with advanced adenoid cystic carcinoma and other tumors. Cancer Res Commun. 2023;3:1853-61.
165. Yuan W, Zhang X, Fan X. The role of the Piezo1 mechanosensitive channel in heart failure. Curr Issues Mol Biol. 2023;45:5830-48.
166. Perryman L, Findlay A, Baskar J, et al. The small molecule LOXL2 inhibitor SNT-5382 reduces cardiac fibrosis and achieves strong clinical target engagement. Sci Rep. 2025;15:22653.
167. Li H, Zhu X, Cao X, Lu Y, Zhou J, Zhang X. Single-cell analysis reveals lysyl oxidase (Lox)+ fibroblast subset involved in cardiac fibrosis of diabetic mice. J Adv Res. 2023;54:223-37.
168. Vasta JD, Andersen KA, Deck KM, Nizzi CP, Eisenstein RS, Raines RT. Selective inhibition of collagen Prolyl 4-hydroxylase in human cells. ACS Chem Biol. 2015;11:193-9.
169. Brandstadter JD, Maillard I. Notch signalling in T cell homeostasis and differentiation. Open Biol. 2019;9:190187.
171. Villanueva MT. Soluble Notch agonists drive T cell production. Nat Rev Drug Discovery. 2025;24:741.
172. Wang J, Xie S, Li N, et al. Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis. Bioact Mater. 2022;17:406-24.
173. Liu J, Wang J, Liu Y, et al. Liquid-liquid phase separation of DDR1 counteracts the hippo pathway to orchestrate arterial stiffening. Circ Res. 2023;132:87-105.
174. Ngai D, Lino M, Rothenberg KE, Simmons CA, Fernandez-Gonzalez R, Bendeck MP. DDR1 (discoidin domain receptor-1)-RhoA (ras homolog family member a) axis senses matrix stiffness to promote vascular calcification. Arterioscler Thromb Vasc Biol. 2020;40:1763-76.
175. Sun X, Wu B, Chiang H, et al. Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion. Nature. 2021;599:673-8.
176. Zhang Y, Duan X, Cao R, et al. Small GTPase RhoA regulates cytoskeleton dynamics during porcine oocyte maturation and early embryo development. Cell Cycle. 2014;13:3390-403.
177. Mejía-ramírez E, Picazo PI, Walter B, et al. Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells. Nat Aging. 2025;6:68-87.
178. Chen K, Griffin M, Henn D, et al. Targeting circulating mechanoresponsive monocytes and macrophages to reduce fibrosis. Nat Biomed Eng. 2025:1479.
179. Kovacs L, Kress TC, Belin De Chantemèle EJ. HIV, Combination Antiretroviral Therapy, and Vascular Diseases in Men and Women. JACC Basic Transl Sci. 2022;7:410-21.
180. Sattentau QJ, Stevenson M. Macrophages and HIV-1: an unhealthy constellation. Cell Host Microbe. 2016;19:304-10.
181. Pang X, He X, Qiu Z, et al. Targeting integrin pathways: mechanisms and advances in therapy. Sig Transduct Target Ther. 2023;8:1.
182. Larsen M, Schmidt-erfurth U, Lanzetta P, et al. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2012;119:992-1000.
183. Amano M, Nakayama M, Kaibuchi K. Rho‐kinase/ROCK: a key regulator of the cytoskeleton and cell polarity. Cytoskeleton. 2010;67:545-54.
184. Lv J, Si T, Wang D, et al. Mechanical signaling via β2 integrin decouples T cell proliferation and differentiation for generating stem cell-like CAR T cells. Immunity. 2025;58:2289-304.e10.
185. Yang J, Savvatis K, Kang JS, et al. Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment. Nat Commun. 2016;7:13710.
186. Poe A, Martinez Yus M, Wang H, Santhanam L. Lysyl oxidase like-2 in fibrosis and cardiovascular disease. Am J Physiol Cell Physiol. 2023;325:C694-707.
187. Wang H, Poe A, Martinez Yus M, Pak L, Nandakumar K, Santhanam L. Lysyl oxidase-like 2 processing by factor Xa modulates its activity and substrate preference. Commun Biol. 2023;6:375.
188. Chaudhari N, Findlay AD, Stevenson AW, et al. Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis. Nat Commun. 2022;13:5555.
189. Taufalele PV, Wang W, Simmons AJ, et al. Matrix stiffness enhances cancer-macrophage interactions and M2-like macrophage accumulation in the breast tumor microenvironment. Acta Biomater. 2023;163:365-77.
190. Rosin NL, Sopel MJ, Falkenham A, Lee TD, Légaré J. Disruption of collagen homeostasis can reverse established age-related myocardial fibrosis. Am J Pathol. 2015;185:631-42.
191. Peacock EE, Madden JW. Administration of beta-aminopropionitrile to human beings with urethral strictures: A preliminary report. Am J Surg. 1978;136:600-5.
192. Keiser HR, Sjoerdsma A. Studies on beta‐aminopropionitrile in patients with scleroderma. Clin Pharmacol Ther. 2016;8:593-602.
193. González A, López B, Ravassa S, San José G, Díez J. The complex dynamics of myocardial interstitial fibrosis in heart failure. Focus on collagen cross-linking. Biochim Biophys Acta Mol Cell Res. 2019;1866:1421-32.
194. Franklin MK, Sawada H, Ito S, et al. β-aminopropionitrile induces distinct pathologies in the ascending and descending thoracic aortic regions of mice. Arterioscler Thromb Vasc Biol. 2024;44:1555-69.
195. Cullen JM, Lu G, Shannon AH, et al. A novel swine model of abdominal aortic aneurysm. J Vasc Surg. 2019;70:252-60.e2.
196. Vachhani P, Baskar J, Charlton B, et al. PXS5505-MF-101: a phase 1/2a study to evaluate safety, pharmacokinetics and pharmacodynamics of Pxs-5505 in patients with primary, post-polycythemia vera or post-essential thrombocythemia myelofibrosis. Blood. 2023;142:625.
197. Zhu Z. Serum LOXL2 is elevated and an independent biomarker in patients with coronary artery disease. Int J Gen Med. 2024;17:4071-80.
198. Frantz S, Störk S, Michels K, et al. Tissue inhibitor of metalloproteinases levels in patients with chronic heart failure: an independent predictor of mortality. Eur J Heart Fail. 2008;10:388-95.
199. Zamilpa R, Ramirez TA, Ibarra J, et al. Abstract 15699: matrix metalloproteinase-9 overexpression in macrophages improves ventricular function by regulating the inflammatory and fibrotic responses post-myocardial infarction. Circulation. 2011;124:A15699.
200. Kobayashi T, Kim H, Liu X, et al. Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels. Am J Physiol Lung Cell Mol Physiol. 2014;306:L1006-15.
201. Froom ZS, Callaghan NI, Davenport Huyer L. Cellular crosstalk in fibrosis: insights into macrophage and fibroblast dynamics. J Biol Chem. 2025;301:110203.
202. Jha G, Sharma RB, Sridhar S, et al. Nanoparticle-based therapies for cardiovascular diseases: a literature review of recent advances and clinical potential. Cureus. 2024;16:e72808.
203. Seth L, Bhave A, Kollapaneni S, et al. Cardiotoxic effects of antibody drug conjugates vs standard chemotherapy in ERBB2-positive advanced breast cancer: a systematic review and meta-analysis. JAMA Netw Open. 2025;8:e2540336.
