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Cited by 21Signaling Pathways in DiseaseCardiovascular, Neuropeptides, and Oxidative Stress ResearchPulmonary Hypertension Research and Treatments

Calcineurin/NFAT Activation-Dependence of Leptin Synthesis and Vascular Growth in Response to Mechanical Stretch

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Soudani, Nadia, Ghantous, Crystal M., Farhat, Zein, Shebaby, Wassim N., Zibara, Kazem, Zeidan, Asad·2016·Frontiers in Physiology
DOI 10.3389/fphys.2016.00433PMC PMC5040753
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Abstract

Background and Aims- Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca+2/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC) hypertrophy and leptin synthesis. Methods and Results- Rat portal vein (RPV) organ culture was used to investigate the effect of mechanical stretch and exogenous leptin (3.1 nM) on VSMC hypertrophy and leptin synthesis. Results showed that stretching the RPV significantly upregulated leptin secretion, mRNA and protein expression, which were inhibited by the calcium channel blocker nifedipine (10 μM), the selective calcineurin inhibitor FK506 (1 nM) and the ERK1/2 inhibitor PD98059 (1 μM). The transcription inhibitor actinomycin D (0.1M) and the translation inhibitor cycloheximide (1 mM) significantly decreased stretch-induced leptin protein expression. Mechanical stretch or leptin caused an increase in wet weight changes and protein synthesis, considered as hypertrophic markers, while they were inhibited by FK506 (0.1 nM; 1 nM). In addition, stretch or exogenous leptin significantly increased calcineurin activity and MCIP1 expression whereas leptin induced NFAT nuclear translocation in VSMCs. Moreover, in response to stretch or exogenous leptin, the Rho inhibitor C3 exoenzyme (30 ng/mL), the ROCK inhibitor Y-27632 (10 μM), and the actin depolymerization agents Latrunculin B (50 nM) and cytochalasin D (1 μM) reduced calcineurin activation and NFAT nuclear translocation. ERK1/2 phosphorylation was inhibited by FK506 and C3. Conclusions- Mechanical stretch-induced VSMC hypertrophy and leptin synthesis and secretion is mediated by Ca2+/calcineurin/NFAT activation. RhoA/ROCK and ERK1/2 activation are critical for mechanical stretch-induced calcineurin activation.

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  • The downstream ROCK target calcineurin can dephosphorylate Drp1 and cause mitochondrial fission.

    “Interestingly, the downstream ROCK target calcineurin can dephosphorylate Drp1 and cause mitochondrial fission [135,136].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [136]

    The Results section on RhoA/ROCK and calcineurin activation (page unavailable) reports that ROCK inhibition reduced calcineurin activity, supporting the downstream relationship under mechanical stretch. The paper discusses calcineurin-mediated NFAT activation, but the searched passages do not address Drp1 dephosphorylation or mitochondrial fission. (LLM, conf=0.87)

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  1. Agata J. Masuda A. Takada M. Higashiura K. Murakami H. Miyazaki Y.. (1997). High plasma immunoreactive leptin level in essential hypertension. Am. J. Hypertens. 10, 1171– 1174. 10.1016/S0895-7061(97)00310-5 9370390 · DOI
  2. Babu G. J. Lalli M. J. Sussman M. A. Sadoshima J. Periasamy M. (2000). Phosphorylation of elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy. J. Mol. Cell. Cardiol. 32, 1447– 1457. 10.1006/jmcc.2000.1185 10900171 · DOI
  3. Bierer R. Nitta C. H. Friedman J. Codianni S. De Frutos S. Dominguez-Bautista J. A.. (2011). NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 301, L872– L880. 10.1152/ajplung.00405.2010 21908592 PMC3233833 · DOI
  4. Bourajjaj M. Armand A. S. Da Costa Martins P. A. Weijts B. Van Der Nagel R. Heeneman S.. (2008). NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure. J. Biol. Chem. 283, 22295– 22303. 10.1074/jbc.M801296200 18477567 · DOI
  5. Bueno O. F. Van Rooij E. Molkentin J. D. Doevendans P. A. De Windt L. J. (2002a). Calcineurin and hypertrophic heart disease: novel insights and remaining questions. Cardiovasc. Res. 53, 806– 821. 10.1016/S0008-6363(01)00493-X 11922891 · DOI
  6. Bueno O. F. Wilkins B. J. Tymitz K. M. Glascock B. J. Kimball T. F. Lorenz J. N.. (2002b). Impaired cardiac hypertrophic response in Calcineurin Abeta-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 99, 4586– 4591. 10.1073/pnas.072647999 11904392 PMC123691 · DOI
  7. Bush E. Fielitz J. Melvin L. Martinez-Arnold M. McKinsey T. A. Plichta R.. (2004). A small molecular activator of cardiac hypertrophy uncovered in a chemical screen for modifiers of the calcineurin signaling pathway. Proc. Natl. Acad. Sci. U.S.A. 101, 2870– 2875. 10.1073/pnas.0308723101 14976250 PMC365712 · DOI
  8. Chien K. R. Knowlton K. U. Zhu H. Chien S. (1991). Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response. FASEB J. 5, 3037– 3046. 1835945
  9. Crabtree G. R. (2001). Calcium, calcineurin, and the control of transcription. J. Biol. Chem. 276, 2313– 2316. 10.1074/jbc.R000024200 11096121 · DOI
  10. Delling U. Tureckova J. Lim H. W. De Windt L. J. Rotwein P. Molkentin J. D. (2000). A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiation and slow myosin heavy-chain expression. Mol. Cell. Biol. 20, 6600– 6611. 10.1128/MCB.20.17.6600-6611.2000 10938134 PMC86143 · DOI
  11. Fernández-Riejos P. Najib S. Santos-Alvarez J. Martín-Romero C. Pérez-Pérez A. González-Yanes C.. (2010). Role of leptin in the activation of immune cells. Mediators Inflamm. 2010: 568343. 10.1155/2010/568343 20368778 PMC2846344 · DOI
  12. Feske S. Okamura H. Hogan P. G. Rao A. (2003). Ca2+/calcineurin signalling in cells of the immune system. Biochem. Biophys. Res. Commun. 311, 1117– 1132. 10.1016/j.bbrc.2003.09.174 14623298 · DOI
  13. Fiedler B. Lohmann S. M. Smolenski A. Linnemuller S. Pieske B. Schroder F.. (2002). Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes. Proc. Natl. Acad. Sci. U.S.A. 99, 11363– 11368. 10.1073/pnas.162100799 12177418 PMC123262 · DOI
  14. Ghantous C. M. Azrak Z. Hanache S. Abou-Kheir W. Zeidan A. (2015a). Differential Role of leptin and adiponectin in cardiovascular system. Int. J. Endocrinol. 2015: 534320. 10.1155/2015/534320 26064110 PMC4433709 · DOI
  15. Ghantous C. M. Kobeissy F. H. Soudani N. Rahman F. A. Al-Hariri M. Itani H. A.. (2015b). Mechanical stretch-induced vascular hypertrophy occurs through modulation of leptin synthesis-mediated ROS formation and GATA-4 nuclear translocation. Front. Pharmacol. 6: 240. 10.3389/fphar.2015.00240 26557089 PMC4615939 · DOI
  16. Gomez M. F. Stevenson A. S. Bonev A. D. Hill-Eubanks D. C. Nelson M. T. (2002). Opposing actions of inositol 1,4,5-trisphosphate and ryanodine receptors on nuclear factor of activated T-cells regulation in smooth muscle. J. Biol. Chem. 277, 37756– 37764. 10.1074/jbc.M203596200 12145283 · DOI
  17. Graef I. A. Chen F. Chen L. Kuo A. Crabtree G. R. (2001). Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 105, 863– 875. 10.1016/S0092-8674(01)00396-8 11439183 · DOI
  18. Herzig T. C. Jobe S. M. Aoki H. Molkentin J. D. Cowley A. W. Jr. Izumo S.. (1997). Angiotensin II type1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload. Proc. Natl. Acad. Sci. U.S.A. 94, 7543– 7548. 10.1073/pnas.94.14.7543 9207128 PMC23858 · DOI
  19. Hill-Eubanks D. C. Gomez M. F. Stevenson A. S. Nelson M. T. (2003). NFAT regulation in smooth muscle. Trends Cardiovasc. Med. 13, 56– 62. 10.1016/S1050-1738(02)00212-8 12586440 · DOI
  20. Hiraoka J. Hosoda K. Ogawa Y. Ikeda K. Nara Y. Masuzaki H.. (1997). Augmentation of obese (ob) gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats). Biochem. Biophys. Res. Commun. 231, 582– 585. 10.1006/bbrc.1997.6145 9070850 · DOI
  21. Hoenig M. R. Bianchi C. Rosenzweig A. Sellke F. W. (2008). The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure. Curr. Vasc. Pharmacol. 6, 292– 300. 10.2174/157016108785909779 18855717 · DOI
  22. Hogan P. G. Chen L. Nardone J. Rao A. (2003). Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17, 2205– 2232. 10.1101/gad.1102703 12975316 · DOI · Paper page
  23. Horsley V. Friday B. B. Matteson S. Kegley K. M. Gephart J. Pavlath G. K. (2001). Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway. J. Cell Biol. 153, 329– 338. 10.1083/jcb.153.2.329 11309414 PMC2169453 · DOI
  24. Hou X. Chen J. Luo Y. Liu F. Xu G. Gao Y. (2013). Silencing of STIM1 attenuates hypoxia-induced PASMCs proliferation via inhibition of the SOC/Ca2+/NFAT pathway. Respir. Res. 14: 2. 10.1186/1465-9921-14-2 23289723 PMC3599439 · DOI
  25. Hsieh Y. L. Tsai Y. L. Shibu M. A. Su C. C. Chung L. C. Pai P.. (2015). ZAK induces cardiomyocyte hypertrophy and brain natriuretic peptide expression via p38/JNK signaling and GATA4/c-Jun transcriptional factor activation. Mol. Cell. Biochem. 405, 1– 9. 10.1007/s11010-015-2389-z 25869677 · DOI
  26. Hullmann J. E. Grisanti L. A. Makarewich C. A. Gao E. Gold J. I. Chuprun J. K.. (2014). GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity. Circ. Res. 115, 976– 985. 10.1161/CIRCRESAHA.116.304475 25332207 PMC4258119 · DOI
  27. Intengan H. D. Schiffrin E. L. (2001). Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension 38, 581– 587. 10.1161/hy09t1.096249 11566935 · DOI · Paper page
  28. Jalil J. Lavandero S. Chiong M. Ocaranza M. P. (2005). [Rho/Rho kinase signal transduction pathway in cardiovascular disease and cardiovascular remodeling]. Rev. Esp. Cardiol. 58, 951– 961. 10.1157/13078132 16053829 · DOI
  29. Karmazyn M. Purdham D. M. Rajapurohitam V. Zeidan A. (2008). Signalling mechanisms underlying the metabolic and other effects of adipokines on the heart. Cardiovasc. Res. 79, 279– 286. 10.1093/cvr/cvn115 18474523 · DOI
  30. Kudryavtseva O. Aalkjaer C. Matchkov V. V. (2013). Vascular smooth muscle cell phenotype is defined by Ca2+-dependent transcription factors. FEBS J. 280, 5488– 5499. 10.1111/febs.12414 23848563 · DOI
  31. Kuhlencordt P. J. Gyurko R. Han F. Scherrer-Crosbie M. Aretz T. H. Hajjar R.. (2001). Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 104, 448– 454. 10.1161/hc2901.091399 11468208 · DOI
  32. Lehoux S. Tedgui A. (1998). Signal transduction of mechanical stresses in the vascular wall. Hypertension 32, 338– 345. 10.1161/01.HYP.32.2.338 9719064 · DOI
  33. Liang F. Gardner D. G. (1999). Mechanical strain activates BNP gene transcription through a p38/NF-kappaB-dependent mechanism. J. Clin. Invest. 104, 1603– 1612. 10.1172/JCI7362 10587524 PMC409860 · DOI
  34. Ljung B. (1990). Vascular selectivity of felodipine: experimental pharmacology. J. Cardiovasc. Pharmacol. 15(Suppl. 4), S11– S16. 10.1097/00005344-199015004-00003 1693715 · DOI
  35. Maffei M. Halaas J. Ravussin E. Pratley R. E. Lee G. H. Zhang Y.. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med. 1, 1155– 1161. 10.1038/nm1195-1155 7584987 · DOI · Paper page
  36. Malmqvist U. Arner A. (1988). Contractile properties during development of hypertrophy of the smooth muscle in the rat portal vein. Acta Physiol. Scand. 133, 49– 61. 10.1111/j.1748-1716.1988.tb08380.x 3227904 · DOI
  37. Malmqvist U. Arner A. (1990). Isoform distribution and tissue contents of contractile and cytoskeletal proteins in hypertrophied smooth muscle from rat portal vein. Circ. Res. 66, 832– 845. 10.1161/01.RES.66.3.832 2306809 · DOI
  38. Margetic S. Gazzola C. Pegg G. G. Hill R. A. (2002). Leptin: a review of its peripheral actions and interactions. Int. J. Obes. Relat. Metab. Disord. 26, 1407– 1433. 10.1038/sj.ijo.0802142 12439643 · DOI
  39. Martínez-Martinez S. Redondo J. M. (2004). Inhibitors of the calcineurin/NFAT pathway. Curr. Med. Chem. 11, 997– 1007. 10.2174/0929867043455576 15078162 · DOI
  40. Molkentin J. D. Lu J. R. Antos C. L. Markham B. Richardson J. Robbins J.. (1998). A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93, 215– 228. 10.1016/S0092-8674(00)81573-1 9568714 PMC4459646 · DOI
  41. Musarò A. McCullagh K. J. Naya F. J. Olson E. N. Rosenthal N. (1999). IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature 400, 581– 585. 10.1038/23060 10448862 · DOI
  42. Nelson T. J. Balza R. Jr. Xiao Q. Misra R. P. (2005). SRF-dependent gene expression in isolated cardiomyocytes: regulation of genes involved in cardiac hypertrophy. J. Mol. Cell. Cardiol. 39, 479– 489. 10.1016/j.yjmcc.2005.05.004 15950986 · DOI
  43. Oka T. Maillet M. Watt A. J. Schwartz R. J. Aronow B. J. Duncan S. A.. (2006). Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ. Res. 98, 837– 845. 10.1161/01.RES.0000215985.18538.c4 16514068 · DOI
  44. Pang X. Sun N. L. (2009). Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation. Acta Pharmacol. Sin. 30, 537– 544. 10.1038/aps.2009.28 19349967 PMC4002815 · DOI
  45. Perego L. Pizzocri P. Corradi D. Maisano F. Paganelli M. Fiorina P.. (2005). Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery: a potential role for leptin in mediating human left ventricular hypertrophy. J. Clin. Endocrinol. Metab. 90, 4087– 4093. 10.1210/jc.2004-1963 15855267 · DOI
  46. Procaccini C. Pucino V. De Rosa V. Marone G. Matarese G. (2014). Neuro-endocrine networks controlling immune system in health and disease. Front. Immunol. 5: 143. 10.3389/fimmu.2014.00143 24778633 PMC3985001 · DOI
  47. Rajapurohitam V. Izaddoustdar F. Martinez-Abundis E. Karmazyn M. (2012). Leptin-induced cardiomyocyte hypertrophy reveals both calcium-dependent and calcium-independent/RhoA-dependent calcineurin activation and NFAT nuclear translocation. Cell. Signal. 24, 2283– 2290. 10.1016/j.cellsig.2012.07.025 22917533 · DOI
  48. Rao A. Luo C. Hogan P. G. (1997). Transcription factors of the NFAT family: regulation and function. Annu. Rev. Immunol. 15, 707– 747. 10.1146/annurev.immunol.15.1.707 9143705 · DOI
  49. Rauch C. Loughna P. T. (2008). Stretch-induced activation of ERK in myocytes is p38 and calcineurin-dependent. Cell Biochem. Funct. 26, 866– 869. 10.1002/cbf.1518 18956431 · DOI
  50. Ren J. Albinsson S. Hellstrand P. (2010). Distinct effects of voltage- and store-dependent calcium influx on stretch-induced differentiation and growth in vascular smooth muscle. J. Biol. Chem. 285, 31829– 31839. 10.1074/jbc.M109.097576 20675376 PMC2951254 · DOI
  51. Roehrl M. H. Kang S. Aramburu J. Wagner G. Rao A. Hogan P. G. (2004). Selective inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with small organic molecules. Proc. Natl. Acad. Sci. U.S.A. 101, 7554– 7559. 10.1073/pnas.0401835101 15131267 PMC419644 · DOI
  52. Saadane N. Alpert L. Chalifour L. E. (1999). Expression of immediate early genes, GATA-4, and Nkx-2.5 in adrenergic-induced cardiac hypertrophy and during regression in adult mice. Br. J. Pharmacol. 127, 1165– 1176. 10.1038/sj.bjp.0702676 10455263 PMC1566134 · DOI
  53. Schäfer K. Halle M. Goeschen C. Dellas C. Pynn M. Loskutoff D. J.. (2004). Leptin promotes vascular remodeling and neointimal growth in mice. Arterioscler. Thromb. Vasc. Biol. 24, 112– 117. 10.1161/01.ATV.0000105904.02142.e7 14615386 · DOI
  54. Schneiderman J. Schaefer K. Kolodgie F. D. Savion N. Kotev-Emeth S. Dardik R.. (2012). Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli. J. Am. Heart Assoc. 1: e001727. 10.1161/JAHA.112.001727 23316287 PMC3541612 · DOI
  55. Seo K. W. Lee S. J. Kim Y. H. Bae J. U. Park S. Y. Bae S. S.. (2013). Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-beta/Akt signaling pathway. PLoS ONE 8: e70437. 10.1371/journal.pone.0070437 23950935 PMC3737227 · DOI
  56. Shyu K. G. (2009). Cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes. Clin. Sci. (Lond). 116, 377– 389. 10.1042/CS20080163 19175356 · DOI
  57. Sinha M. K. Opentanova I. Ohannesian J. P. Kolaczynski J. W. Heiman M. L. Hale J.. (1996). Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J. Clin. Invest. 98, 1277– 1282. 10.1172/JCI118913 8823291 PMC507552 · DOI
  58. Stenvinkel P. (2000). Leptin and blood pressure–is there a link? Nephrol. Dial. Transplant. 15, 1115– 1117. 10.1093/ndt/15.8.1115 10910430 · DOI
  59. Sutter M. C. (1990). The mesenteric-portal vein in research. Pharmacol. Rev. 42, 287– 325. 2080226
  60. Suzuki E. Nishimatsu H. Satonaka H. Walsh K. Goto A. Omata M.. (2002). Angiotensin II induces myocyte enhancer factor 2- and calcineurin/nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes. Circ. Res. 90, 1004– 1011. 10.1161/01.RES.0000017629.70769.CC 12016267 · DOI
  61. Takeda Y. Yoneda T. Demura M. Usukura M. Mabuchi H. (2002). Calcineurin inhibition attenuates mineralocorticoid-induced cardiac hypertrophy. Circulation 105, 677– 679. 10.1161/hc0602.104675 11839620 · DOI
  62. Turczynska K. M. Sadegh M. K. Hellstrand P. Swärd K. Albinsson S. (2012). MicroRNAs are essential for stretch-induced vascular smooth muscle contractile differentiation via microRNA (miR)-145-dependent expression of L-type calcium channels. J. Biol. Chem. 287, 19199– 19206. 10.1074/jbc.M112.341073 22474293 PMC3365952 · DOI
  63. Waitkus-Edwards K. R. Martinez-Lemus L. A. Wu X. Trzeciakowski J. P. Davis M. J. Davis G. E.. (2002). alpha(4) beta(1) Integrin activation of L-type calcium channels in vascular smooth muscle causes arteriole vasoconstriction. Circ. Res. 90, 473– 480. 10.1161/hh0402.105899 11884378 · DOI
  64. Wilkins B. J. Molkentin J. D. (2004). Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem. Biophys. Res. Commun. 322, 1178– 1191. 10.1016/j.bbrc.2004.07.121 15336966 · DOI
  65. Yang J. Rothermel B. Vega R. B. Frey N. McKinsey T. A. Olson E. N.. (2000). Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ. Res. 87, E61– E68. 10.1161/01.RES.87.12.e61 11110780 · DOI
  66. Zeidan A. Broman J. Hellstrand P. Swärd K. (2003a). Cholesterol dependence of vascular ERK1/2 activation and growth in response to stretch: role of endothelin-1. Arterioscler. Thromb. Vasc. Biol. 23, 1528– 1534. 10.1161/01.ATV.0000090129.75275.C2 12907462 · DOI
  67. Zeidan A. Javadov S. Karmazyn M. (2006). Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating leptin-induced hypertrophy in rat neonatal ventricular myocytes. Cardiovasc. Res. 72, 101– 111. 10.1016/j.cardiores.2006.06.024 16901475 · DOI
  68. Zeidan A. Karmazyn M. (2006). Leptin and vascular smooth muscle. Curr. Vasc. Pharmacol. 4, 383– 393. 10.2174/157016106778521634 17073703 · DOI
  69. Zeidan A. Nordström I. Albinsson S. Malmqvist U. Swärd K. Hellstrand P. (2003b). Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors. Am. J. Physiol. Cell Physiol. 284, C1387– C1396. 10.1152/ajpcell.00508.2002 12734104 · DOI
  70. Zeidan A. Nordström I. Dreja K. Malmqvist U. Hellstrand P. (2000). Stretch-dependent modulation of contractility and growth in smooth muscle of rat portal vein. Circ. Res. 87, 228– 234. 10.1161/01.RES.87.3.228 10926874 · DOI
  71. Zeidan A. Paylor B. Steinhoff K. J. Javadov S. Rajapurohitam V. Chakrabarti S.. (2007). Actin cytoskeleton dynamics promotes leptin-induced vascular smooth muscle hypertrophy via RhoA/ROCK- and phosphatidylinositol 3-kinase/protein kinase B-dependent pathways. J. Pharmacol. Exp. Ther. 322, 1110– 1116. 10.1124/jpet.107.122440 17562852 · DOI
  72. Zeidan A. Purdham D. M. Rajapurohitam V. Javadov S. Chakrabarti S. Karmazyn M. (2005). Leptin induces vascular smooth muscle cell hypertrophy through angiotensin II- and endothelin-1-dependent mechanisms and mediates stretch-induced hypertrophy. J. Pharmacol. Exp. Ther. 315, 1075– 1084. 10.1124/jpet.105.091561 16144973 · DOI
  73. Zuure W. A. Roberts A. L. Quennell J. H. Anderson G. M. (2013). Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function. J. Neurosci. 33, 17874– 17883. 10.1523/JNEUROSCI.2278-13.2013 24198376 PMC6618430 · DOI

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Authors
Soudani, N., Ghantous, C. M., Farhat, Z., Shebaby, W. N., Zibara, K., & Zeidan, A.
Affiliations
  • American University of Beirut (LB)
  • Lebanese American University (LB)
  • Lebanese University (LB)
Corresponding author
Zeidan, Asad
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2016-09-29
Volume
7
Pages
433-433
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2016.00433
PMC
PMC5040753
OpenAlex
W2527456393
Cited by
21
References
2
Citations by year
2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 2
FWCI
0.87
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords
leptin, calcineurin, NFAT, vascular smooth muscle hypertrophy, mechanical stretch, RhoA/ROCK signaling, ERK1/2 phosphorylation, calcium signaling, portal vein, hypertension, obesity, vascular development, nifedipine, FK506, PD98059, actin cytoskeleton, leptin secretion

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