Changes of Thyroid Hormone Receptor Activity in Patients with Hypertensive Non-valvular Atrial Fibrillation_West China Medical Journal

Authors：

WANG Si , HE Sen ,  CHEN Xiaoping , WAN Liyan , LI Longxin

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

CHEN Xiaoping, Email: qijing2788@126.com

Keywords：

高血压; 非瓣膜心房颤动; 甲状腺激素受体活性

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目的　研究高血压非瓣膜心房颤动患者甲状腺激素受体（TR）的活性差异，以探讨此类患者心房颤动发生发展的可能机制。方法　2008年1月－2010年1月序贯收集103例高血压非瓣膜心房颤动患者的相关资料（48例阵发性心房颤动、55例持续性心房颤动），并收集50例单纯高血压患者。收集各组患者的相关人口学数据及检查结果，并采用放射性分析技术测定各组患者外周血淋巴细胞及淋巴细胞核TR的活性，主要包括平衡解离常数（Kd）及最大结合容量（MBC）。结果　心房颤动患者淋巴细胞TR的Kd较单纯高血压患者小（越小表示与甲状腺激素的亲和力越高），且持续性心房颤动患者的Kd较阵发性心房颤动患者更小（0.77 ± 0.43、1.02 ± 0.41，P＜0.001）；心房颤动患者淋巴细胞TR的MBC较单纯高血压患者小(越小表示受体总量越少)，且持续性心房颤动患者TR的MBC较阵发性心房颤动患者更小（36.10 ± 12.40、65.22 ± 30.90，P＜0.001）。淋巴细胞核TR的Kd及MBC也存在类似情况。简单相关分析提示左房直径与淋巴细胞TR的Kd及MBC呈负相关，另外，调整相关指标后偏相关分析也提示左房直径与Kd及MBC呈负相关（Kd：r=?0.296，MBC：r=?0.448；P均＜0.01）；淋巴细胞核TR的Kd及MBC也存在类似情况。结论　高血压非瓣膜心房颤动患者中，TR的总量减少，并且持续心房颤动组低于阵发心房颤动组；甲状腺激素与受体的亲和力在心房颤动患者中升高，且持续心房颤动组高于阵发心房颤动组。另外，还发现TR的Kd和MBC与左房直径均呈负相关。这些改变可能是高血压非瓣膜心房颤动患者心房颤动发生及维持的一种重要机制。

Citation： WANG Si,HE Sen,CHEN Xiaoping,WAN Liyan,LI Longxin. Changes of Thyroid Hormone Receptor Activity in Patients with Hypertensive Non-valvular Atrial Fibrillation. West China Medical Journal, 2012, 27(4): 512-516. doi: Copy

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10.	Watanabe H, Ma M, Washizuka T, et al. Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium[J]. Biochem Bioph Res Co, 2003, 308(3): 439-444.
11.	Chen XP, Bing Z, He J, et al. Downregulation of peroxisome proliferator-activated receptor-γ expression in hypertensive atrial fibrillation[J]. Clin Cardiol, 2009, 32(6): 337-345.
12.	Parkash R, Green MS, Kerr CR, et al. The association of left atrial size and occurrence of atrial fibrillation: a prospective cohort study from the canadian registry of atrial fibrillation[J]. Am Heart J, 2004, 148(4): 649-654.
13.	Psaty BM, Manolio TA, Kuller LH, et al. Incidence of and risk factors for atrial fibrillation in older adults[J]. Circulation, 1997, 96(7): 2455-2461.
14.	Zhang J, Lazar MA. The mechanism of action of thyroid hormones[J]. Ann Rev Physiol, 2000, 62(3): 439-466.
15.	Yen PM. Physiological and molecular basis of thyroid hormone action[J]. Physiol Re, 2001, 81(3): 1097-1142.
16.	Yen PM, Feng X, Flamant F, et al. Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice[J]. EMBO Rep, 2003, 4 (6): 581-587.
17.	Johnson PN, Freedberg AS, Marshall JM. Action of thyroid hormone on the transmembrane potentials from sinoatrial node cells and atrial muscle cells in isolated atria of rabbits[J]. Cardiology, 1973, 58(5): 273-289.
18.	Watanabe H, Ma M, Washizuka T, et al. Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium[J]. Biochem Bioph Res Co, 2003, 308(3): 439-444.
19.	Basset A, Blanc J, Messas E, et al. Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: an echocardiographic study[J]. J Cardiovasc Pharmacol, 2001, 37(2): 163-172.
20.	Hu LW, Benvenuti LA, Liberti EA, et al. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling[J]. Am J Physiol Regul Integr Comp Physiol, 2003, 285(6): R1473-1480.
21.	Iglesias P, Diez JJ. Influence of thyroid dysfunction on serum concentrations of adipocytokines[J]. Cytokine, 2007, 40(2): 61-70.

1. 　Wolf PA, Dawber TR, Thomas HE Jr, et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham Study[J]. Neurology, 1978, 28(10): 973-977.
2. 　Krahn AD, Manfreda J, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba follow-up study[J]. Am J Med, 1995, 98(5): 476-484.
3. 　van Wagoner DR. Oxidative stress and inflammation in atrial fibrillation:role in pathogenesis and potential as a therapeutic target[J]. J Cardiovasc Pharmacol, 2008, 52(4): 306-313.
4. 　Kourliouros A, Savelieva I, Kiotsekoglou A, et al. Current concepts in the pathogenesis of atrial fibrillation[J]. Am Heart J, 2009, 157(2): 243-252.
5. 　Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons[J]. N Engl J Med, 1994, 331(19): 1249-1252.
6. 　Auer J, Scheibner P, Mische T, et al. Subclinical hyperthyroidism as a risk factor for atrial fibrillation[J]. Am Heart J, 2001, 142(5): 838-842.
7. 　Forfar JC, Miller HC, Toft AD. Occult thyrotoxicosis: a correctable cause of “idiopathic” atrial fibrillation[J]. Am J Cardiol, 1979, 44(1): 9-12.
8. 　Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrialfibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation)[J]. Eur Heart J, 2006, 27(16):1979-2030.
9. 　Krahn AD, Klein GJ, Kerr CR, et al. How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian registry of atrial fibrillation investigators[J]. Arch Intern Med, 1996, 156(19): 2221-2224.
10. 　Watanabe H, Ma M, Washizuka T, et al. Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium[J]. Biochem Bioph Res Co, 2003, 308(3): 439-444.
11. 　Chen XP, Bing Z, He J, et al. Downregulation of peroxisome proliferator-activated receptor-γ expression in hypertensive atrial fibrillation[J]. Clin Cardiol, 2009, 32(6): 337-345.
12. 　Parkash R, Green MS, Kerr CR, et al. The association of left atrial size and occurrence of atrial fibrillation: a prospective cohort study from the canadian registry of atrial fibrillation[J]. Am Heart J, 2004, 148(4): 649-654.
13. 　Psaty BM, Manolio TA, Kuller LH, et al. Incidence of and risk factors for atrial fibrillation in older adults[J]. Circulation, 1997, 96(7): 2455-2461.
14. 　Zhang J, Lazar MA. The mechanism of action of thyroid hormones[J]. Ann Rev Physiol, 2000, 62(3): 439-466.
15. 　Yen PM. Physiological and molecular basis of thyroid hormone action[J]. Physiol Re, 2001, 81(3): 1097-1142.
16. 　Yen PM, Feng X, Flamant F, et al. Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice[J]. EMBO Rep, 2003, 4 (6): 581-587.
17. 　Johnson PN, Freedberg AS, Marshall JM. Action of thyroid hormone on the transmembrane potentials from sinoatrial node cells and atrial muscle cells in isolated atria of rabbits[J]. Cardiology, 1973, 58(5): 273-289.
18. 　Watanabe H, Ma M, Washizuka T, et al. Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium[J]. Biochem Bioph Res Co, 2003, 308(3): 439-444.
19. 　Basset A, Blanc J, Messas E, et al. Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: an echocardiographic study[J]. J Cardiovasc Pharmacol, 2001, 37(2): 163-172.
20. 　Hu LW, Benvenuti LA, Liberti EA, et al. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling[J]. Am J Physiol Regul Integr Comp Physiol, 2003, 285(6): R1473-1480.
21. 　Iglesias P, Diez JJ. Influence of thyroid dysfunction on serum concentrations of adipocytokines[J]. Cytokine, 2007, 40(2): 61-70.

West China Medical Journal

Changes of Thyroid Hormone Receptor Activity in Patients with Hypertensive Non-valvular Atrial Fibrillation

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