REFERENCES
1. Yu Z, Gong H, Kesteven S, et al. Piezo1 is the cardiac mechanosensor that initiates the cardiomyocyte hypertrophic response to pressure overload in adult mice. Nat Cardiovasc Res. 2022;1:577-91.
2. Lim GB. Piezo1 senses pressure overload and initiates cardiac hypertrophy. Nat Rev Cardiol. 2022;19:503-503.
3. Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 2018;15:387-407.
5. Mackrill JJ, Shiels HA. Evolution of excitation-contraction coupling. In: Islam MS, editors. Calcium Signaling. Cham: Springer International Publishing; 2019. pp. 281-320.
6. Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 2006;7:589-600.
7. Zhang M, Ma Y, Ye X, Zhang N, Pan L, Wang B. TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases. Sig Transduct Target Ther. 2023;8:261.
8. Jin C, Su S, Yu S, et al. Essential roles of PIEZO1 in mammalian cardiovascular system: from development to diseases. Cells. 2024;13:1422.
9. Soda T, Brunetti V, Berra-Romani R, Moccia F. The emerging role of N-methyl-D-aspartate (NMDA) receptors in the cardiovascular system: physiological implications, pathological consequences, and therapeutic perspectives. Int J Mol Sci. 2023;24:3914.
10. Rossi MA, Carillo SV. Cardiac hypertrophy due to pressure and volume overload: distinctly different biological phenomena? Int J Cardiol. 1991;31:133-41.
11. Papapostolou S, Kearns J, Costello BT, et al. Comparison of pressure vs volume overload ventricular wall stress in patients with valvular heart disease. J Am Coll Cardiol. 2024;84:635-44.
12. Goonasekera SA, Hammer K, Auger-Messier M, et al. Decreased cardiac L-type Ca2+ channel activity induces hypertrophy and heart failure in mice. J Clin Investig. 2012;122:280-90.
13. Ruwhof C. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res. 2000;47:23-37.
14. Zou Y, Akazawa H, Qin Y, et al. Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol. 2004;6:499-506.
15. Veteto AB, Peana D, Lambert MD, Mcdonald KS, Domeier TL. Transient receptor potential vanilloid-4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart. Cardiovasc Res. 2020;116:1887-96.
16. Izu LT, Kohl P, Boyden PA, et al. Mechano-electric and mechano-chemo-transduction in cardiomyocytes. J Physiol. 2020;598:1285-305.
17. Davis MJ, Earley S, Li Y, Chien S. Vascular mechanotransduction. Physiol Rev. 2023;103:1247-421.
18. Nourse JL, Pathak MM. How cells channel their stress: Interplay between Piezo1 and the cytoskeleton. Semin Cell Dev Biol. 2017;71:3-12.
19. Uray IP, Uray K. Mechanotransduction at the plasma membrane-cytoskeleton interface. Int J Mol Sci. 2021;22:11566.
20. Casarella S, Ferla F, Di Francesco D, Canciani E, Rizzi M, Boccafoschi F. Focal adhesion’s role in cardiomyocytes function: from cardiomyogenesis to mechanotransduction. Cells. 2024;13:664.
21. Chuang Y, Chen C. Force from filaments: the role of the cytoskeleton and extracellular matrix in the gating of mechanosensitive channels. Front Cell Dev Biol. 2022;10:886048.
22. Viola HM, Hool LC. The L-type Ca2+ channel: a mediator of hypertrophic cardiomyopathy. Channels. 2016;11:5-7.
23. Tang W, Strachan RT, Lefkowitz RJ, Rockman HA. Allosteric modulation of β-arrestin-biased angiotensin II type 1 receptor signaling by membrane stretch. J Biol Chem. 2014;289:28271-83.
24. Brown DI, Griendling KK. Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res. 2015;116:531-49.
25. Elias-Llumbet A, Sharmin R, Berg-Sorensen K, Schirhagl R, Mzyk A. The interplay between mechanoregulation and ROS in heart physiology, disease, and regeneration. Adv Healthc Mater. 2024;13:2400952.
26. Wan E, Abrams J, Weinberg RL, et al. Aberrant sodium influx causes cardiomyopathy and atrial fibrillation in mice. J Clin Investig. 2015;126:112-22.
27. Kohlhaas M, Liu T, Knopp A, et al. Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes. Circulation. 2010;121:1606-13.
28. Erickson JR, Joiner MA, Guan X, et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell. 2008;133:462-74.
29. Terentyev D, Györke I, Belevych AE, et al. Redox modification of ryanodine receptors contributes to sarcoplasmic reticulum Ca2+ leak in chronic heart failure. Circ Res. 2008;103:1466-72.
30. Yoshida T, Inoue R, Morii T, et al. Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol. 2006;2:596-607.
31. Kitajima N, Numaga-Tomita T, Watanabe M, et al. TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling. Sci Rep. 2016;6:37001.
32. Kuwahara K, Wang Y, Mcanally J, et al. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Investig. 2006;116:3114-26.
33. Du J, Xie J, Zhang Z, et al. TRPM7-mediated Ca2+ signals confer fibrogenesis in human atrial fibrillation. Circ Res. 2010;106:992-1003.
34. Adapala RK, Thoppil RJ, Luther DJ, et al. TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals. J Mol Cell Cardiol. 2013;54:45-52.
35. Emig R, Knodt W, Krussig MJ, et al. Piezo1 channels contribute to the regulation of human atrial fibroblast mechanical properties and matrix stiffness sensing. Cells. 2021;10:663.
36. He Y, Zhang H, Zhang Q, et al. NMDA-type glutamate receptor activation promotes ischemic arrhythmias by targeting the AKT1-TBX3-Nav1.5 axis. Acta Physiol. 2025;241:e70085.
37. Ramirez RJ, Sah R, Liu J, Rose RA, Backx PH. Intracellular [Na+] modulates synergy between Na+/Ca2+ exchanger and L-type Ca2+ current in cardiac excitation-contraction coupling during action potentials. Basic Res Cardiol. 2011;106:967-77.
38. Hofmann F, Flockerzi V, Kahl S, Wegener JW. L-type CaV1.2 calcium channels: from in vitro findings to in vivo function. Physiol Rev. 2014;94:303-26.
39. Treinys R, Jurevičius J. L-type Ca2+ channels in the heart: Structure and regulation. Medicina. 2008;44:491.
40. Pallien T, Klussmann E. New aspects in cardiac L-type Ca2+ channel regulation. Biochem Soc Trans. 2020;48:39-49.
41. Gao H, Wang F, Wang W, et al. Ca2+ influx through L-type Ca2+ channels and transient receptor potential channels activates pathological hypertrophy signaling. J Mol Cell Cardiol. 2012;53:657-67.
42. Tonegawa K, Otsuka W, Kumagai S, et al. Caveolae-specific activation loop between CaMKII and L-type Ca2+ channel aggravates cardiac hypertrophy in α1-adrenergic stimulation. Am J Physiol Heart Circ Physiol. 2017;312:H501-14.
43. Tandan S, Wang Y, Wang TT, et al. Physical and functional interaction between calcineurin and the cardiac L-type Ca2+ channel. Circ Res. 2009;105:51-60.
44. Pedrozo Z, Criollo A, Battiprolu PK, et al. Polycystin-1 is a cardiomyocyte mechanosensor that governs L-type Ca2+ channel protein stability. Circulation. 2015;131:2131-42.
45. Manning JR, Yin G, Kaminski CN, et al. Rad GTPase deletion increases L-type calcium channel current leading to increased cardiac contraction. J Am Heart Assoc. 2013;2:e000459.
46. Li M, He H, Gong H, et al. NFATc4 and myocardin synergistically up-regulate the expression of LTCC α1C in ET-1-induced cardiomyocyte hypertrophy. Life Sci. 2016;155:11-20.
47. Ahern BM, Levitan BM, Veeranki S, et al. Myocardial-restricted ablation of the GTPase RAD results in a pro-adaptive heart response in mice. J Biol Chem. 2019;294:10913-27.
48. Viola H, Johnstone V, Cserne Szappanos H, et al. The L-type Ca2+ channel facilitates abnormal metabolic activity in the cTnI-G203S mouse model of hypertrophic cardiomyopathy. J Physiol. 2016;594:4051-70.
49. Er TS, Reinke D, Francis AJ, et al. Novel peptide therapeutics targeting the L-type calcium channel prevent hypertrophic cardiomyopathy by decreasing mitochondrial energetics. JACC Basic Transl Sci. 2025;10:101292.
50. Kobayashi T, Kurebayashi N, Murayama T. The ryanodine receptor as a sensor for intracellular environments in muscles. Int J Mol Sci. 2021;22:10795.
51. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol Cell Physiol. 1983;245:C1-C14.
52. Waddell HM, Mereacre V, Alvarado FJ, Munro ML. Clustering properties of the cardiac ryanodine receptor in health and heart failure. J Mol Cell Cardiol. 2023;185:38-49.
53. Wang S, Song L, Lakatta EG, Cheng H. Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells. Nature. 2001;410:592-6.
54. Pan W, Hunkler HJ, Chatterjee S, et al. A circular RNA derived from the ryanodine receptor 2 locus controls cardiac hypertrophy and calcium handling. Cell Mol Life Sci. 2025;82:359.
55. Gez LS, Hagalili Y, Shainberg A, Atlas D. Voltage-driven Ca2+ binding at the L-type Ca2+ channel triggers cardiac excitation-contraction coupling prior to Ca2+ influx. Biochemistry. 2012;51:9658-66.
56. Zou Y, Liang Y, Gong H, et al. Ryanodine receptor type 2 is required for the development of pressure overload-induced cardiac hypertrophy. Hypertension. 2011;58:1099-110.
57. Van Oort RJ, Respress JL, Li N, et al. Accelerated development of pressure overload-induced cardiac hypertrophy and dysfunction in an RyR2-R176Q knockin mouse model. Hypertension. 2010;55:932-8.
58. Pogwizd SM, Schlotthauer K, Li L, Yuan W, Bers DM. Arrhythmogenesis and contractile dysfunction in heart failure: roles of sodium-calcium exchange, inward rectifier potassium current, and residual β-adrenergic responsiveness. Circ Res. 2001;88:1159-67.
59. Shigekawa M, Iwamoto T. Cardiac Na+-Ca2+ exchange: molecular and pharmacological aspects. Circ Res. 2001;88:864-76.
60. Fleig A, Penner R. The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends Pharmacol Sci. 2004;25:633-9.
61. Nishida M, Kurose H. Roles of TRP channels in the development of cardiac hypertrophy. Naunyn Schmiedebergs Arch Pharmacol. 2008;378:395-406.
62. Grimm M, Brown JH. β-adrenergic receptor signaling in the heart: role of CaMKII. J Mol Cell Cardiol. 2010;48:322-30.
63. Ohba T, Watanabe H, Murakami M, et al. Upregulation of TRPC1 in the development of cardiac hypertrophy. J Mol Cell Cardiol. 2007;42:498-507.
64. Seo K, Rainer PP, Shalkey Hahn V, et al. Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proc Natl Acad Sci USA. 2014;111:1551-6.
65. Sonkusare SK, Bonev AD, Ledoux J, et al. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012;336:597-601.
66. Katanosaka Y, Iwasaki K, Ujihara Y, et al. TRPV2 is critical for the maintenance of cardiac structure and function in mice. Nat Commun. 2014;5:3932.
67. Zhang Q, Qi H, Cao Y, et al. Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats. J Cell Mol Med. 2018;22:6055-67.
68. Horton JS, Buckley CL, Stokes AJ. Successful TRPV1 antagonist treatment for cardiac hypertrophy and heart failure in mice. Channels. 2014;7:17-22.
69. Wang H, Wang W, Cornish KG, Rozanski GJ, Zucker IH. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure. Hypertension. 2014;64:745-55.
70. Guo Y, Yu Z, Wu J, et al. The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy. eLife. 2021;10:e66582.
71. Sah R, Mesirca P, Mason X, et al. Timing of myocardial Trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization. Circulation. 2013;128:101-14.
72. Chubanov V, Köttgen M, Touyz RM, Gudermann T. TRPM channels in health and disease. Nat Rev Nephrol. 2023;20:175-87.
73. Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330:55-60.
74. Cox CD, Bae C, Ziegler L, et al. Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat Commun. 2016;7:10366.
75. Wu J, Lewis AH, Grandl J. Touch, tension, and transduction - the function and regulation of Piezo ion channels. Trends Biochem Sci. 2017;42:57-71.
76. Jiang F, Yin K, Wu K, et al. The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction. Nat Commun. 2021;12:869.
77. Zhang Y, Su S, Li W, et al. Piezo1-mediated mechanotransduction promotes cardiac hypertrophy by impairing calcium homeostasis to activate calpain/calcineurin signaling. Hypertension. 2021;78:647-60.
78. Bartoli F, Evans EL, Blythe NM, et al. Global PIEZO1 gain-of-function mutation causes cardiac hypertrophy and fibrosis in mice. Cells. 2022;11:1199.
79. Li J, Hou B, Tumova S, et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014;515:279-82.
80. Ranade SS, Qiu Z, Woo S, et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci USA. 2014;111:10347-52.
81. Gill SS, Pulido OM, Mueller RW, Mcguire PF. Molecular and immunochemical characterization of the ionotropic glutamate receptors in the rat heart. Brain Res Bull. 1998;46:429-34.
82. Zarei MM, Dani JA. Ionic permeability characteristics of the N-methyl-D-aspartate receptor channel. J Gen Physiol. 1994;103:231-48.
83. Tu Y, Yang Y, Kuo C. Modulation of NMDA channel gating by Ca2+ and Cd2+ binding to the external pore mouth. Sci Rep. 2016;6:37029.
84. Amin JB, Leng X, Gochman A, Zhou H, Wollmuth LP. A conserved glycine harboring disease-associated mutations permits NMDA receptor slow deactivation and high Ca2+ permeability. Nat Commun. 2018;9:3748.
85. Shi S, Liu T, Li Y, et al. Chronic N-methyl-d-aspartate receptor activation induces cardiac electrical remodeling and increases susceptibility to ventricular arrhythmias. Pacing Clin Electrophysiol. 2014;37:1367-77.
86. Gao X, Xu X, Pang J, et al. NMDA receptor activation induces mitochondrial dysfunction, oxidative stress and apoptosis in cultured neonatal rat cardiomyocytes. Physiol Res. ;2007:559-69.
87. Santulli G, Xie W, Reiken SR, Marks AR. Mitochondrial calcium overload is a key determinant in heart failure. Proc Natl Acad Sci USA. 2015;112:11389-94.
88. Moshal K, Metreveli N, Frank I, Tyagi S. Mitochondrial MMP activation, dysfunction and arrhythmogenesis in hyperhomocysteinemia. Curr Vasc Pharmacol. 2008;6:84-92.
89. Repas SJ, Saad NS, Janssen PML, Elnakish MT. Memantine, an NMDA receptor antagonist, prevents thyroxin-induced hypertension, but not cardiac remodeling. J Cardiovasc Pharmacol. 2017;70:305-13.
90. Earley S, Brayden JE. Transient receptor potential channels in the vasculature. Physiol Rev. 2015;95:645-90.
91. Solano AS, Lavanderos B, Metwally E, Earley S. Transient receptor potential channels in vascular mechanotransduction. Am J Hypertens. 2025;38:151-60.
92. Earley S, Waldron BJ, Brayden JE. Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ Res. 2004;95:922-9.
93. Retailleau K, Duprat F, Arhatte M, et al. Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling. Cell Rep. 2015;13:1161-71.
94. Blythe NM, Muraki K, Ludlow MJ, et al. Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion. J Biol Chem. 2019;294:17395-408.
95. Solis AG, Bielecki P, Steach HR, et al. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature. 2019;573:69-74.
96. Falcón D, Galeano-Otero I, Martín-Bórnez M, et al. TRPC channels: dysregulation and Ca2+ mishandling in ischemic heart disease. Cells. 2020;9:173.
97. Jia M, Liu W, Zhang K, et al. Larixyl acetate, a TRPC6 inhibitor, attenuates pressure overload‑induced heart failure in mice. Mol Med Rep. 2024;29:49.
98. Kinoshita H, Kuwahara K, Nishida M, et al. Inhibition of TRPC6 channel activity contributes to the antihypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart. Circ Res. 2010;106:1849-60.
99. Thorneloe KS, Cheung M, Bao W, et al. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012;4:159ra148.
100. Syeda R, Xu J, Dubin AE, et al. Chemical activation of the mechanotransduction channel Piezo1. eLife. 2015;4:e07369.
101. Suchyna TM, Johnson JH, Hamer K, et al. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol. 2000;115:583-98.
102. Evans EL, Cuthbertson K, Endesh N, et al. Yoda1 analogue (D ooku1) which antagonizesY oda1-evoked activation ofP iezo1 and aortic relaxation. Br J Pharmacol. 2018;175:1744-59.
103. Elliott WJ, Ram CVS. Calcium channel blockers: calcium channel blockers. J Clin Hypertens. 2011;13:687-9.
104. Frishman WH. Calcium channel blockers: differences between subclasses. Am J Cardiovasc Drugs. 2007;7:17-23.
105. Godfraind T. Calcium channel blockers in cardiovascular pharmacotherapy. J Cardiovasc Pharmacol Ther. 2014;19:501-15.
106. Weir MR. Calcium Channel blockers: their pharmacologic and therapeutic role in hypertension. Am J Cardiovasc Drugs. 2007;7:5-15.
107. Zhu J, Chen N, Zhou M, et al. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database Syst Rev. 2022:2022.
108. Eisenberg MJ, Brox A, Bestawros AN. Calcium channel blockers: an update. Am J Med. 2004;116:35-43.
110. Rafe MR, Saha P, Bello ST. Targeting NMDA receptors with an antagonist is a promising therapeutic strategy for treating neurological disorders. Behav Brain Res. 2024;472:115173.
111. Zambrano P, Suwalsky M, Jemiola-Rzeminska M, Strzalka K. Studies on the interaction of NMDA receptor antagonist memantine with cell membranes: a mini-review. Chem Biol Interact. 2018;283:47-50.
112. Abbaszadeh S, Javidmehr A, Askari B, Janssen PM, Soraya H. Memantine, an NMDA receptor antagonist, attenuates cardiac remodeling, lipid peroxidation and neutrophil recruitment in heart failure: a cardioprotective agent? Biomed Pharmacother. 2018;108:1237-43.
113. Ghafouri-Asbagh A, Tabatabaei K, Vaez H, et al. Memantine, an NMDA receptor antagonist, attenuates doxorubicin-induced cardiac oxidative stress and inflammation in mouse 4T1 breast cancer model. Breast Cancer. 2025;19:11782234251393421.
114. Kobayashi S, Yano M, Suetomi T, et al. Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor. J Am Coll Cardiol. 2009;53:1993-2005.
115. Gao Y, Li S, Liu X, et al. RyR2 stabilizer attenuates cardiac hypertrophy by downregulating TNF-α/NF-κB/NLRP3 signaling pathway through inhibiting calcineurin. J Cardiovasc Transl Res. 2024;17:481-95.
116. Tanaka H, Nishimaru K, Aikawa T, Hirayama W, Tanaka Y, Shigenobu K. Effect of SEA0400, a novel inhibitor of sodium-calcium exchanger, on myocardial ionic currents. Br J Pharmacol. 2009;135:1096-100.
117. Dai D, Chen T, Szeto H, et al. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol. 2011;58:73-82.
118. Dikalova AE, Bikineyeva AT, Budzyn K, et al. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res. 2010;107:106-16.
