Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2014

Open Access 01-12-2014 | Research article

Implication of plasma intermedin levels in patients who underwent first-time diagnostic coronary angiography: a single centre, cross-sectional study

Authors: Aylin Hatice Yamac, Ahmet Bacaksiz, Ziya Ismailoglu, Sitki Kucukbuzcu, Emrah Sevgili, Emin Asoglu, Muharrem Nasifov, Parviz Jafarov, Ercan Erdogan, Omer Goktekin

Published in: BMC Cardiovascular Disorders | Issue 1/2014

Login to get access

Abstract

Background

Intermedin (IMD) is involved in the prevention of atherosclerotic plaque progression, possessing cardioprotective effects from hypertrophy, fibrosis and ischemia-reperfusion injury. Elevated plasma IMD levels have been demonstrated in patients with acute coronary syndromes. No human study has examined the role of IMD in stable patients who underwent diagnostic coronary angiography with suspicion of coronary artery disease (CAD). Thus we investigated the role of IMD as a biomarker to discriminate patients with CAD and predict those with severe disease who require early and intensive therapeutic intervention before presenting with acute coronary syndrome.

Methods

Eligible two hundred and thirty-eight consecutive patients (123 males, mean age 58.4 ± 10.0 years) who underwent first-time diagnostic coronary angiography were included in this study. Plasma concentrations of IMD were measured from arterial blood samples by the enzyme-linked immunosorbent assay. Patients were divided into three groups according to the presence and degree of CAD, consisting of 48 patients with normal coronary anatomy (Group 1), 111 patients with < 50% coronary stenosis (Group 2), and 79 patients with ≥ 50% stenosis in at least one of the major coronary arteries (group 3). The severity and extent of CAD was evaluated by calculations of the vessel, Gensini, and SYNTAX scores.

Results

Circulating plasma IMD levels in patients with CAD were significantly higher than those in patients without CAD (157.7 ± 9.6, 134.8 ± 11.9, and 117.6 ± 7.9 pg/mL in groups 3, 2 and 1 respectively; p < 0.001). Besides, plasma IMD levels were correlated with Gensini and SYNTAX scores (rs = 0.742, and rs = 0.296, respectively; p < 0.05). The presence of ≥50% coronary artery stenosis could be predicted if a cut-off value of 147.7 pg/mL for plasma IMD was used with 88.6% sensitivity and 88.7% specificity. Moreover, a plasma IMD level of <126.6 pg/mL could discriminate a patient with normal coronary arteries from patients with angiographically proven CAD with a sensitivity and specificity of 84.7%, and 83.3% respectively.

Conclusions

We demonstrated that IMD might be used as a biomarker to predict CAD and its severity in patients who underwent first time diagnostic coronary angiography.
Appendix
Available only for authorised users
Literature
1.
go back to reference Nürnberger J, Kribben A, Philipp T, Erbel R: Arterial compliance (stiffness) as a marker of subclinical atherosclerosis. Herz. 2007, 32 (5): 379-386. 10.1007/s00059-007-3030-z.CrossRefPubMed Nürnberger J, Kribben A, Philipp T, Erbel R: Arterial compliance (stiffness) as a marker of subclinical atherosclerosis. Herz. 2007, 32 (5): 379-386. 10.1007/s00059-007-3030-z.CrossRefPubMed
2.
go back to reference Hansson GK, Robertson AK, Söderberg-Nauclér C: Inflammation and atherosclerosis. Annu Rev Pathol. 2006, 1: 297-329. 10.1146/annurev.pathol.1.110304.100100.CrossRefPubMed Hansson GK, Robertson AK, Söderberg-Nauclér C: Inflammation and atherosclerosis. Annu Rev Pathol. 2006, 1: 297-329. 10.1146/annurev.pathol.1.110304.100100.CrossRefPubMed
3.
go back to reference Giannotti G, Landmesser U: Endothelial dysfunction as an early sign of atherosclerosis. Herz. 2007, 32 (7): 568-572. 10.1007/s00059-007-3073-1.CrossRefPubMed Giannotti G, Landmesser U: Endothelial dysfunction as an early sign of atherosclerosis. Herz. 2007, 32 (7): 568-572. 10.1007/s00059-007-3073-1.CrossRefPubMed
4.
go back to reference Libby P, Ridker PM, Hansson GK: Leducq transatlantic network on atherothrombosis: inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009, 54 (23): 2129-2138. 10.1016/j.jacc.2009.09.009.CrossRefPubMedPubMedCentral Libby P, Ridker PM, Hansson GK: Leducq transatlantic network on atherothrombosis: inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009, 54 (23): 2129-2138. 10.1016/j.jacc.2009.09.009.CrossRefPubMedPubMedCentral
5.
go back to reference Pan CS, Yang JH, Cai DY, Zhao J, Gerns H, Yang J, Chang JK, Tang CS, Qi YF: Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2. Peptides. 2005, 26 (9): 1640-1646. 10.1016/j.peptides.2005.02.013.CrossRefPubMed Pan CS, Yang JH, Cai DY, Zhao J, Gerns H, Yang J, Chang JK, Tang CS, Qi YF: Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2. Peptides. 2005, 26 (9): 1640-1646. 10.1016/j.peptides.2005.02.013.CrossRefPubMed
6.
go back to reference Bell D, McDermott BJ: Intermedin (adrenomedullin-2): a novel counter-regulatory peptide in the cardiovascular and renal systems. Br J Pharmacol. 2008, 153 (Suppl 1): S247-S262.PubMed Bell D, McDermott BJ: Intermedin (adrenomedullin-2): a novel counter-regulatory peptide in the cardiovascular and renal systems. Br J Pharmacol. 2008, 153 (Suppl 1): S247-S262.PubMed
7.
go back to reference Yang X, Zhang H, Jia Y, Ni L, Li G, Xue L, Jiang Y: Effects of intermedin1-53 on myocardial fibrosis. Acta Biochim Biophys Sin (Shanghai). 2013, 45 (2): 141-148. 10.1093/abbs/gms093.CrossRef Yang X, Zhang H, Jia Y, Ni L, Li G, Xue L, Jiang Y: Effects of intermedin1-53 on myocardial fibrosis. Acta Biochim Biophys Sin (Shanghai). 2013, 45 (2): 141-148. 10.1093/abbs/gms093.CrossRef
8.
go back to reference Zhao L, Peng DQ, Zhang J, Song JQ, Teng X, Yu YR, Tang CS, Qi YF: Extracellular signal-regulated kinase 1/2 activation is involved in intermedin1-53 attenuating myocardial oxidative stress injury induced by ischemia/reperfusion. Peptides. 2012, 33 (2): 329-335. 10.1016/j.peptides.2011.12.016.CrossRefPubMed Zhao L, Peng DQ, Zhang J, Song JQ, Teng X, Yu YR, Tang CS, Qi YF: Extracellular signal-regulated kinase 1/2 activation is involved in intermedin1-53 attenuating myocardial oxidative stress injury induced by ischemia/reperfusion. Peptides. 2012, 33 (2): 329-335. 10.1016/j.peptides.2011.12.016.CrossRefPubMed
9.
go back to reference Zhang X, Gu L, Chen X, Wang S, Deng X, Liu K, Lv Z, Yang R, He S, Peng Y, Huang D, Jiang W, Wu K: Intermedin ameliorates atherosclerosis in ApoE null mice by modifying lipid profiles. Peptides. 2012, 37 (2): 189-193. 10.1016/j.peptides.2012.07.011.CrossRefPubMed Zhang X, Gu L, Chen X, Wang S, Deng X, Liu K, Lv Z, Yang R, He S, Peng Y, Huang D, Jiang W, Wu K: Intermedin ameliorates atherosclerosis in ApoE null mice by modifying lipid profiles. Peptides. 2012, 37 (2): 189-193. 10.1016/j.peptides.2012.07.011.CrossRefPubMed
10.
go back to reference Qin YW, Teng X, He JQ, Du J, Tang CS, Qi YF: Increased plasma levels of intermedin and brain natriuretic peptide associated with severity of coronary stenosis in acute coronary syndrome. Peptides. 2013, 42: 84-88.CrossRefPubMed Qin YW, Teng X, He JQ, Du J, Tang CS, Qi YF: Increased plasma levels of intermedin and brain natriuretic peptide associated with severity of coronary stenosis in acute coronary syndrome. Peptides. 2013, 42: 84-88.CrossRefPubMed
11.
go back to reference Lv Z, Wu K, Chen X, Zhang X, Hong B: Plasma intermedin levels in patients with acute myocardial infarction. Peptides. 2013, 43: 121-125.CrossRefPubMed Lv Z, Wu K, Chen X, Zhang X, Hong B: Plasma intermedin levels in patients with acute myocardial infarction. Peptides. 2013, 43: 121-125.CrossRefPubMed
12.
go back to reference Gensini GG: A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983, 51 (3): 606-10.1016/S0002-9149(83)80105-2.CrossRefPubMed Gensini GG: A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983, 51 (3): 606-10.1016/S0002-9149(83)80105-2.CrossRefPubMed
13.
go back to reference Sullivan DR, Marwick TH, Freedman SB: A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J. 1990, 119 (6): 1262-1267. 10.1016/S0002-8703(05)80173-5.CrossRefPubMed Sullivan DR, Marwick TH, Freedman SB: A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J. 1990, 119 (6): 1262-1267. 10.1016/S0002-8703(05)80173-5.CrossRefPubMed
14.
go back to reference Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW: The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005, 1 (2): 219-227.PubMed Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW: The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005, 1 (2): 219-227.PubMed
15.
go back to reference Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972, 18 (6): 499-502.PubMed Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972, 18 (6): 499-502.PubMed
16.
go back to reference Roh J, Chang CL, Bhalla A, Klein C, Hsu SY: Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes. J Biol Chem. 2004, 279 (8): 7264-7274.CrossRefPubMed Roh J, Chang CL, Bhalla A, Klein C, Hsu SY: Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes. J Biol Chem. 2004, 279 (8): 7264-7274.CrossRefPubMed
17.
go back to reference Hinson JP, Kapas S, Smith DM: Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000, 21 (2): 138-167.PubMed Hinson JP, Kapas S, Smith DM: Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000, 21 (2): 138-167.PubMed
18.
go back to reference Bell D, Zhao Y, McCoy FP, Devine A, McDermott BJ: Expression of the counter-regulatory peptide intermedin is augmented in the presence of oxidative stress in hypertrophied cardiomyocytes. Cell Physiol Biochem. 2008, 21 (5–6): 409-420.CrossRefPubMed Bell D, Zhao Y, McCoy FP, Devine A, McDermott BJ: Expression of the counter-regulatory peptide intermedin is augmented in the presence of oxidative stress in hypertrophied cardiomyocytes. Cell Physiol Biochem. 2008, 21 (5–6): 409-420.CrossRefPubMed
19.
go back to reference Hirose T, Totsune K, Mori N, Morimoto R, Hashimoto M, Nakashige Y, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Sasano H, Kohzuki M, Takahashi K, Imai Y: Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure. Eur J Heart Fail. 2008, 10 (9): 840-849. 10.1016/j.ejheart.2008.06.020.CrossRefPubMed Hirose T, Totsune K, Mori N, Morimoto R, Hashimoto M, Nakashige Y, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Sasano H, Kohzuki M, Takahashi K, Imai Y: Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure. Eur J Heart Fail. 2008, 10 (9): 840-849. 10.1016/j.ejheart.2008.06.020.CrossRefPubMed
20.
go back to reference Bell D, Campbell M, Ferguson M, Sayers L, Donaghy L, O’Regan A, Jewhurst V, Harbinson M: AM(1)-receptor-dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia-reperfusion injury. J Physiol. 2012, 590 (Pt 5): 1181-1197.CrossRefPubMed Bell D, Campbell M, Ferguson M, Sayers L, Donaghy L, O’Regan A, Jewhurst V, Harbinson M: AM(1)-receptor-dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia-reperfusion injury. J Physiol. 2012, 590 (Pt 5): 1181-1197.CrossRefPubMed
21.
go back to reference Du QX, Yue W, Wang YY: Effect and mechanism of intermedin in acute rat cardiac ischemic injury. Fa yi xue za zhi. 2011, 27 (3): 164-168.PubMed Du QX, Yue W, Wang YY: Effect and mechanism of intermedin in acute rat cardiac ischemic injury. Fa yi xue za zhi. 2011, 27 (3): 164-168.PubMed
22.
go back to reference Teng X, Song J, Zhang G, Cai Y, Yuan F, Du J, Tang C, Qi Y: Inhibition of endoplasmic reticulum stress by intermedin(1–53) protects against myocardial injury through a PI3 kinase-Akt signaling pathway. J Mol Med (Berl). 2011, 89 (12): 1195-1205. 10.1007/s00109-011-0808-5.CrossRef Teng X, Song J, Zhang G, Cai Y, Yuan F, Du J, Tang C, Qi Y: Inhibition of endoplasmic reticulum stress by intermedin(1–53) protects against myocardial injury through a PI3 kinase-Akt signaling pathway. J Mol Med (Berl). 2011, 89 (12): 1195-1205. 10.1007/s00109-011-0808-5.CrossRef
23.
go back to reference Song JQ, Teng X, Cai Y, Tang CS, Qi YF: Activation of Akt/GSK-3beta signaling pathway is involved in intermedin(1–53) protection against myocardial apoptosis induced by ischemia/reperfusion. Apoptosis. 2009, 14 (11): 1299-1307. 10.1007/s10495-009-0398-7.CrossRefPubMed Song JQ, Teng X, Cai Y, Tang CS, Qi YF: Activation of Akt/GSK-3beta signaling pathway is involved in intermedin(1–53) protection against myocardial apoptosis induced by ischemia/reperfusion. Apoptosis. 2009, 14 (11): 1299-1307. 10.1007/s10495-009-0398-7.CrossRefPubMed
Metadata
Title
Implication of plasma intermedin levels in patients who underwent first-time diagnostic coronary angiography: a single centre, cross-sectional study
Authors
Aylin Hatice Yamac
Ahmet Bacaksiz
Ziya Ismailoglu
Sitki Kucukbuzcu
Emrah Sevgili
Emin Asoglu
Muharrem Nasifov
Parviz Jafarov
Ercan Erdogan
Omer Goktekin
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2014
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/1471-2261-14-182

Other articles of this Issue 1/2014

BMC Cardiovascular Disorders 1/2014 Go to the issue