Nongenomic actions of thyroid hormone and the cardiovascular function

Abstract

Abstract: Thyroid hormones play a wide range of important physiological activities in almost all organism. As changes in these hormones levels, observed in hypothyroidism and hyperthyroidism, promote serious derangements of the cardiovascular system, it is important to know their mechanisms of actions. Although the classic genomic actions which are dependent on interaction with nuclear receptors to modulate cardiac myocyte genes expression, there is growing evidence about T₃ and T₄-triggered nongenomic pathways, resulting from their binding to plasma membrane, cytoplasm, or mitochondrial receptors that leads to a rapid regulation of cardiovascular functions. Disappointedly, little attention is paid to the rapid nongenomic actions of thyroid hormones on cardiovascular system. This paper reviews the effects of thyroid hormones on cardiovascular function via nongenomic actions involving extranuclear receptors, second messengers, or effect proteins. A full understanding of the link between thyroid hormones and cardiovascular functions should be beneficial for appropriate management of cardiovascular diseases by modulating thyroid hormones levels.

Key words: Thyroid hormones, Nongenomic action, Cardiovascular function

CLC Number:

R977.1⁺4

YAN Xiao-lin, PENG Jun, DING Qi-long. Nongenomic actions of thyroid hormone and the cardiovascular function[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(5): 586-591.

References

[1] Sabatino L, Colantuoni A, Iervasi G. Is the vascular system a main target for thyroid hormones? From molecular and biochemical findings to clinical perspectives[J]. Curr vasc Pharmacol, 2005, 3(2): 133-145.
[2] Chanoine JP, Braverman LE, Farwell AP, et al. The thyroid gland is a major source of circulating T3 in the rat[J]. J Clin Invest, 1993, 91(6): 2709-2713.
[3] Sabatino L, Chopra IJ, Tanavoli S, et al. A radioimmunoassay for type Ι iodothyronine 5'-monodeiodinase in human tissues[J]. Thyroid, 2001, 11(8): 733-739.
[4] Gereben B,Zavacki AM, Ribich S, et al. Cellular and molecular basis of deiodinase regulated thyroid hormone signaling[J]. Endocr Rev, 2008, 29(7): 898-938.
[5] Trivieri MG, Oudit GY, Sah R, et al. Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction[J]. Proc Natl Acad Sci USA, 2006,103(15): 6043-6048.
[6] Liu Y, Redetzke RA, Said S, et al. Serum thyroid hormone levels may not accurately reflect thyroid tissue levels and cardiac function in mild hypothyroidism[J]. Am J Physiol Heart Circ Physiol, 2008, 294(5): H2137-H2143.
[7] Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system[J]. N Engl J Med, 2001, 344(7): 501-509.
[8] Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease[J]. Endocrine, 2004, 24(1): 1-13.
[9] Wang YG, Dedkova EN, Fiening JP, et al. Acute exposure to thyroid hormone increases Na⁺ currentandintracellular Ca²⁺ in cat atrial myocytes[J]. J Physiol, 2003, 546(2): 491-499.
[10] Kuzman JA, Vogelsang KA, Thomas TA, et al. L-Thyroxine activates Akt signaling in the heart[J]. J Mol Cell Cardiol, 2005, 39(2): 251-258.
[11] Kenessey A, Ojamaa K. Thyroid hormone stimulates protein synthesis in the cardiomyocyte by activating the Akt-mTOR and p70s6k pathways[J]. J Biol Chem, 2006, 281(7): 20666-20672.
[12] Storey NM, Gentile S, Ullah H, et al. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone[J]. Proc Natl Acad Sci USA, 2006, 103(13): 5197-5201.
[13] Zinman T, Shneyvays V, Tribulova N, et al. Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes[J]. J Cell Physiol, 2006,207(1): 220-231.
[14] Farach-Carson MC, Davis PJ. Steroid hormone interactions with target cells: Cross talk between membrane and nuclear pathways[J]. J Pharmacol Exp Ther, 2003, 307(3): 839-845.
[15] Saelim N, John LM, Wu J, et al. Nontranscriptional modulation of intercellular Ca²⁺ signaling by ligand stimulated thyroid hormone receptor[J].J Cell Biol, 2004, 167(5): 915-924.
[16] Bergh JJ, Lin HY, Lansing L, et al. Intergrin αvβ3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis[J]. Endocrinology, 2005, 146(7): 2864-2871.
[17] Cody V, Davis PJ, Davis FB. Molecular modeling of the thyroid hormone interactions with αvβ3 integrin[J]. Steroids, 2007, 72(2): 165-170.
[18] Davis PJ, Davis FB, Lin HY, et al. Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor[J]. Am J Physiol Endocrinol Metab, 2009, 297(6): E1238-E1246.
[19] Lin HY, Sun M, Tang HY, et al. L-Thyroxine vs. 3, 5, 3' -triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase[J]. Am J Physiol Cell Physiol, 2009, 296(5): C980-C991.
[20] Bassett JH, Harvey CB, Williams GR. Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions[J]. Mol Cell Endocrinol, 2003, 213(1): 1-11.
[21] Lin HY, Tang HY, Shih A, et al. Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic[J]. Steroids, 2007, 72(2): 180-187.
[22] Lin HY, Tang HY, Keating T, et al. Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: Both actions are integrin and ERK mediated[J]. Carcinogenesis, 2008, 29(1): 62-69.
[23] Hiroi Y, Kim HH, Ying H, et al. Rapid nongenomic actions of thyroid hormone[J]. Proc Natl Acad Sci USA, 2006, 103(38): 14104-14109.
[24] Lei J, Mariash CN, Ingbar DH. 3, 3', 5-Triiodo-L-thyronine up-regulation of Na,K-ATPase activity and cell surface expression in alveolar epithelial cells is Scr kinase and phosphoinositide 3-kinase- dependent[J]. J Biol Chem, 2004, 279(46): 47589-47600.
[25] Schmidt BM, Martin N, Georgens AC, et al. Nongenomic cardiovascular effects of triiodothyronine in euthyroid male volunteers[J]. J Clin Endocrinol Metab, 2002, 87(4): 1681-1686.
[26] Zarain-Herzberg A, Estrada-Avilés R, Fraqoso-Medina J. Regulation of sarco(endo) plasmic reticulum Ca²⁺-ATPase and calsequestrin gene expression in the heart[J]. Can J Physiol Pharmacol, 2012, 90(8): 1017-1028.
[27] Watanabe H, Washizuka T, Komura S, et al. Genomic and nonfenomic regulation of L-type calcium channels in rat ventricle by thyroid hormone[J]. Endocr Res, 2005, 31(1): 59-70.
[28] 方放治, 戴德哉. 甲状腺素对心脏离子通道和转运装置的影响[J]. 中国临床药理学与治疗学, 2002, 7(2): 177-180.
[29] Pantos C, Xinaris C, Mourouzis I, et al. Thyroid hormone changes cardiomyocyte shape and geometry via ERK signaling pathway: Potential therapeutic implications in reversing cardiac remodeling[J] ? Mol Cell Biochem, 2007, 297(1/2): 65-72.
[30] Mitasikova M, Lin H, Soukup T, et al. Diabetes and thyroid hormones affect connexin-43 and PKC-e expression in rat heart atria[J]. Physiol Res, 2009, 58(2): 211-217.
[31] Sakaguchi Y, Cui G, Sen L. Acute effects of thyroid hormone on inward rectifier potassium channel currents in guinea pig ventricular myocytes[J]. Endocrinology, 1996, 137(11): 4744-4751.
[32] Sun ZQ, Ojamaa K, Coetzee WA, et al. Effects of thyroid hormone on action potential an repolarizing currents in rat ventricular myocytes[J]. Am J Physiol, 2000, 278(2): E302-E307.
[33] Doohan MM, Gray DF, Hool LC, et al. Thyroid status and regulation of intracellular sodium in rabbit heart[J]. Am J Physiol, 1997, 272(4): H1589-H1597.
[34] 戴德哉. 心律失常, 离子通道病及新药发现[J]. 中国临床药理学与治疗学, 2006, 11(9): 961-965.
[35] Avkiran M. Rational basis for use of sodium-hydrogen exchange inhibiters in myocardial ischemia[J]. Am J Cardiol, 1999, 83(10): 10G-18G.
[36] Fujio Y, Nguyen T, Wencher D, et al. Akt promotes survival of cardiomyocytes in vitro an protects against ischemia-reperfusion injury in mouse heart[J]. Circulation, 2000, 101(6): 660-667.
[37] Furuya F, Lu C, Guigon CJ, et al. Nongenomic action of phosphatidylinositol 3-kinase signaling by thyroid hormone receptors[J]. Steroids, 2009, 74(7): 628-634.
[38] Quesada A, Sainz J, Wangensteen R, et al. Nitric oxide synthase activity in hyperthyroid and hypothyroid rats[J]. Eur J Endocrinol, 2002, 147(1): 117-122.
[39] Carrillo-Sepúlveda MA, Ceravolo GS, Fortes ZB, et al. Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes[J]. Cardiovasc Res, 2010, 85(3): 560-570.
[40] Moreno JM, Wangensteen R, Sainz J, et al. Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats[J]. Am J Physiol, 2003, 285(1): E182-E188.
[41] Xiao Z, Zhang Z, Diamond SL. Shear stress induction of the endothelial nitric oxide synthase gene is calcium dependent but not calcium-activation[J]. J Cell Physiol, 1997, 171(2): 205-211.
[42] Chakrabarti N, Ray AK. Rise of intrasynaptosomal Ca²⁺ level and activation of nitric oxide synthase in adult rat cerebral cortex pretreated with 3-5-3' -L-triiodothyronine[J]. Neuropsychopharmacology, 2000, 22(1): 36-41.
[43] Hirata Y, Hayakawa H, Suzuki E, et al. Direct measurement of endothelium-derived nitric oxide release by stimulation of endothelin receptors in rat kidney an its alterations in salt induced hypertension[J]. Circulation, 1995, 91(4): 1229-1235.
[44] Singh G, Thompson EB, Gulati A. Altered endothelin 1 concentration in the brain and peripheral regions during thyroid dysfunction[J]. Pharmacology, 1994, 49(3): 184-191.
[45] Park KW, Dai HB, Ojamaa K, et al. The direct vasomotor effect of thyroid hormones on rat skeletal muscle resistance arteries[J]. Anesth Analg, 1997, 85(4): 734-738.