Relationship Between Intermedin and Atrial Fibrosis in Patients of Hypertension Combined with Atrial Fibrillation_Journal of Biomedical Engineering

Authors：

FENGJiayue ,  CHENXiaoping , WANLiyan , HESen , ZHOUYufei , WANShixi

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

Corresponding author：

CHENXiaoping, Email: chenxp13@aliyun.com

Keywords：

intermedin; atrial fibrillation; transforming growth factor β1; atrial fibrosis

DOI：

10.7507/1001-5515.20140206

Video：

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This study was aimed to evaluate the relationship between the changes of plasma intermedin (IMD) and atrial fibrosis in hypertensive patients with atrial fibrillation. During the period from 2010 to 2011, appropriate 150 subjects of out-patients (female 50%,male 50%) were selected in West China Hospital, Sichuan University, and were divided into three groups: the hypertension-only group, the hypertension combined with paroxysmal atrial fibrillation group and the hypertension combined with persistent atrial fibrillation group. Firstly, we collected the Physical examination results and medical history records of the patients. We then performed ultrasound cardiogram and blood biochemical tests on the patients. We also detected the plasma IMD and transforming growth factor β1(TGF-β1) using ELISA. The results showed that compared with the hypertensive group, the plasma level of IMD, TGF-β1 and left atrium director (LAD) in the hypertensive combined with atrial fibrillation group were higher significantly. Compared with the paroxymal atrial fibrillation group, the levels of IMD, TGF-β1 and LAD were higher significantly in persistent atrial fibrillation group. Analysis of correlation and partial correlation showed that IMD was positively correlated with TGF-β1 (r=0.51, P<0.001), IMD was positively correlated with LAD(r=0.59, P<0.001), and TGF-β1 was positively correlated with LAD (r=0.57, P<0.001). The results suggest that IMD might suppress the pathophysiological process of atrial fibrillation.

Citation： FENGJiayue, CHENXiaoping, WANLiyan, HESen, ZHOUYufei, WANShixi. Relationship Between Intermedin and Atrial Fibrosis in Patients of Hypertension Combined with Atrial Fibrillation. Journal of Biomedical Engineering, 2014, 31(5): 1097-1101,1110. doi: 10.7507/1001-5515.20140206 Copy

1.	LIP G Y, TSE H F. Management of atrial fibrillation[J]. Lancet, 2007, 370(9587): 604-618.
2.	HAÏSSAGUERRE M, JAÏS P, SHAH D C, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins[J]. N Engl J Med, 1998, 339(10): 659-666.
3.	ALLESSIE M, AUSMA J, SCHOTTEN U. Electrical, contractile and structural remodeling during atrial fibrillation[J]. Cardiovasc Res, 2002, 54(2): 230-246.
4.	BURSTEIN B, NATTEl S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation[J]. J Am Coll Cardiol, 2008, 51(8): 802-809.
5.	ECKSTEIN J, VERHEULE S, DE GROOT N M, et al. Mechanisms of perpetuation of atrial fibrillation in chronically dilated atria[J]. Prog Biophys Mol Biol, 2008, 97(2-3): 435-451.
6.	LIJNEN P J, PETROV V V, FAGARD R H. Induction of cardiac fibrosis by transforming growth factor-beta(1)[J]. Mol Genet Metab, 2000, 71(1-2): 418-435.
7.	ROH J, CHANG C L, BHALLA A, et al. Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes[J]. J Biol Chem, 2004, 279(8): 7264-7274.
8.	TAKEI Y, INOUE K, OGOSHI M, et al. Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator[J]. FEBS Lett, 2004, 556(1-3): 53-58.
9.	KINDT F, WIEGAND S, LÖSER C, et al. Intermedin: a skin peptide that is downregulated in atopic dermatitis[J]. J Invest Dermatol, 2007, 127(3): 605-613.
10.	MORIMOTO R, SATOH F, MURAKAMI O, et al. Expression of adrenomedullin2/intermedin in human brain, heart, and kidney[J]. Peptides, 2007, 28(5): 1095-1103.
11.	REN Y S, YANG J H, ZHANG J, et al. Intermedin 1-53 in central nervous system elevates arterial blood pressure in rats[J]. Peptides, 2006, 27(1): 74-79.
12.	PAN C S, YANG J H, CAI D Y, et al. Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2[J]. Peptides, 2005, 26(9): 1640-1646.
13.	FUJISAWA Y, NAGAI Y, MIYATAKE A, et al. Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats[J]. Am J Physiol Heart Circ Physiol, 2006, 290(3): 1120-1127.
14.	FUJISAWA Y, NAGAI Y, MIYATAKE A, et al. Renal effects of a new member of adrenomedullin family, adrenomedullin2, in rats[J]. Eur J Pharmacol, 2004, 497(1): 75-80.
15.	HAGIWARA M, BLEDSOE G, YANG Z R, et al. Intermedin ameliorates vascular and renal injury by inhibition of oxidative stress[J]. Am J Physiol Renal Physiol, 2008, 295(6): 1735-1743.
16.	YANG J H, CAI Y, DUAN X H, et al. Intermedin 1-53 inhibits rat cardiac fibroblast activation induced by angiotensin II[J]. Regul Pept, 2009, 158(1-3): 19-25.
17.	MANSIA G, DE BACKER G, DOMINICZAK A, et al. 2007 ESH-ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC)[J]. Eur Heart J, 2007, 16(3): 135-232.
18.	WANN L S, CURTIS A B, JANUARY C T, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J]. Circulation, 2011, 8(1): 157-176.
19.	POTPARA T S, LIP G Y. Lone atrial fibrillation: what is known and what is to come[J]. Int J Clin Pract, 2011, 65(4): 446-457.
20.	NAKAJIMA H, NAKAJIMA H O, SALCHER O, et al. Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1)transgene in the heart[J]. Circ Res, 2000, 86(5): 571-579.
21.	VERHEULE S, SATO T, EVERETT T, et al. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1[J]. Circ Res, 2004, 94(11): 1458-1465.
22.	BURSTEIN B, LIBBY E, CALDERONE A, et al. Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial-ventricular remodeling differences[J]. Circulation, 2008, 117(13): 1630-1641.
23.	CHOI E K, CHANG P C, LEE Y S, et al. Triggered firing and atrial fibrillation in transgenic mice with selective atrial fibrosis induced by overexpression of TGF-β1[J]. Circ J, 2012, 76(6): 1354-1362.
24.	CASACLANG-VERZOSA G, GERSH B J, TSANG T S. Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation[J]. J Am Coll Cardiol, 2008, 51(1): 1-11.
25.	ON Y K, JEON E S, LEE S Y, et al. Plasma transforming growth factor beta1 as a biochemical marker to predict the persistence of atrial fibrillation after the surgical maze procedure[J]. J Thorac Cardiovasc Surg, 2009, 137(6): 1515-1520.
26.	CHEN X, BING Z, HE J, et al. Downregulation of peroxisome proliferator-activated receptor-gamma expression in hypertensive atrial fibrillation[J]. Clin Cardiol, 2009, 32(6): 337-345.

1. LIP G Y, TSE H F. Management of atrial fibrillation[J]. Lancet, 2007, 370(9587): 604-618.
2. HAÏSSAGUERRE M, JAÏS P, SHAH D C, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins[J]. N Engl J Med, 1998, 339(10): 659-666.
3. ALLESSIE M, AUSMA J, SCHOTTEN U. Electrical, contractile and structural remodeling during atrial fibrillation[J]. Cardiovasc Res, 2002, 54(2): 230-246.
4. BURSTEIN B, NATTEl S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation[J]. J Am Coll Cardiol, 2008, 51(8): 802-809.
5. ECKSTEIN J, VERHEULE S, DE GROOT N M, et al. Mechanisms of perpetuation of atrial fibrillation in chronically dilated atria[J]. Prog Biophys Mol Biol, 2008, 97(2-3): 435-451.
6. LIJNEN P J, PETROV V V, FAGARD R H. Induction of cardiac fibrosis by transforming growth factor-beta(1)[J]. Mol Genet Metab, 2000, 71(1-2): 418-435.
7. ROH J, CHANG C L, BHALLA A, et al. Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes[J]. J Biol Chem, 2004, 279(8): 7264-7274.
8. TAKEI Y, INOUE K, OGOSHI M, et al. Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator[J]. FEBS Lett, 2004, 556(1-3): 53-58.
9. KINDT F, WIEGAND S, LÖSER C, et al. Intermedin: a skin peptide that is downregulated in atopic dermatitis[J]. J Invest Dermatol, 2007, 127(3): 605-613.
10. MORIMOTO R, SATOH F, MURAKAMI O, et al. Expression of adrenomedullin2/intermedin in human brain, heart, and kidney[J]. Peptides, 2007, 28(5): 1095-1103.
11. REN Y S, YANG J H, ZHANG J, et al. Intermedin 1-53 in central nervous system elevates arterial blood pressure in rats[J]. Peptides, 2006, 27(1): 74-79.
12. PAN C S, YANG J H, CAI D Y, et al. Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2[J]. Peptides, 2005, 26(9): 1640-1646.
13. FUJISAWA Y, NAGAI Y, MIYATAKE A, et al. Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats[J]. Am J Physiol Heart Circ Physiol, 2006, 290(3): 1120-1127.
14. FUJISAWA Y, NAGAI Y, MIYATAKE A, et al. Renal effects of a new member of adrenomedullin family, adrenomedullin2, in rats[J]. Eur J Pharmacol, 2004, 497(1): 75-80.
15. HAGIWARA M, BLEDSOE G, YANG Z R, et al. Intermedin ameliorates vascular and renal injury by inhibition of oxidative stress[J]. Am J Physiol Renal Physiol, 2008, 295(6): 1735-1743.
16. YANG J H, CAI Y, DUAN X H, et al. Intermedin 1-53 inhibits rat cardiac fibroblast activation induced by angiotensin II[J]. Regul Pept, 2009, 158(1-3): 19-25.
17. MANSIA G, DE BACKER G, DOMINICZAK A, et al. 2007 ESH-ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC)[J]. Eur Heart J, 2007, 16(3): 135-232.
18. WANN L S, CURTIS A B, JANUARY C T, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J]. Circulation, 2011, 8(1): 157-176.
19. POTPARA T S, LIP G Y. Lone atrial fibrillation: what is known and what is to come[J]. Int J Clin Pract, 2011, 65(4): 446-457.
20. NAKAJIMA H, NAKAJIMA H O, SALCHER O, et al. Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1)transgene in the heart[J]. Circ Res, 2000, 86(5): 571-579.
21. VERHEULE S, SATO T, EVERETT T, et al. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1[J]. Circ Res, 2004, 94(11): 1458-1465.
22. BURSTEIN B, LIBBY E, CALDERONE A, et al. Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial-ventricular remodeling differences[J]. Circulation, 2008, 117(13): 1630-1641.
23. CHOI E K, CHANG P C, LEE Y S, et al. Triggered firing and atrial fibrillation in transgenic mice with selective atrial fibrosis induced by overexpression of TGF-β1[J]. Circ J, 2012, 76(6): 1354-1362.
24. CASACLANG-VERZOSA G, GERSH B J, TSANG T S. Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation[J]. J Am Coll Cardiol, 2008, 51(1): 1-11.
25. ON Y K, JEON E S, LEE S Y, et al. Plasma transforming growth factor beta1 as a biochemical marker to predict the persistence of atrial fibrillation after the surgical maze procedure[J]. J Thorac Cardiovasc Surg, 2009, 137(6): 1515-1520.
26. CHEN X, BING Z, HE J, et al. Downregulation of peroxisome proliferator-activated receptor-gamma expression in hypertensive atrial fibrillation[J]. Clin Cardiol, 2009, 32(6): 337-345.

Journal of Biomedical Engineering

Relationship Between Intermedin and Atrial Fibrosis in Patients of Hypertension Combined with Atrial Fibrillation

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