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Erschienen in: Inflammation Research 5/2014

01.05.2014 | Original Research Paper

The effect of prolonged systemic doxycycline therapy on serum tissue degrading proteinases in coronary bypass patients: a randomized, double-masked, placebo-controlled clinical trial

verfasst von: Immi Kormi, Hatem Alfakry, Taina Tervahartiala, Pirkko J. Pussinen, Juha Sinisalo, Timo Sorsa

Erschienen in: Inflammation Research | Ausgabe 5/2014

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Abstract

Objective

Serum matrix metalloproteinases (MMP-8, MMP-7) and their regulators may be associated with the risk of incident cardiovascular disease events. Doxycycline can be used as matrix metalloproteinase (MMP) inhibitor independent of its antimicrobial activity. We aimed to investigate serum inflammatory biomarkers during 4 months of doxycycline therapy in coronary bypass patients.

Materials and methods

Thirty-one non-smoking men who had previous coronary bypass surgery were randomly assigned to receive placebo or 100 mg doxycycline daily for 4 months. Serum samples were collected at baseline before the treatment, and at 2, 4, and 10 months. Serum levels of MMP-7, tissue inhibitor of matrix metalloproteinase (TIMP)-1, myeloperoxidase, and neutrophil elastase were analyzed with enzyme-linked immunosorbent assay, MMP-8 by immunofluorometric assay, and C-reactive protein by rate nephelometry.

Results

At baseline, no significant differences existed between the two groups. Serum levels of MMP-8, MMP-7, and MMP-8/TIMP-1 were and remained lower (p = 0.034, p = 0.041, and NS) in the doxycycline group relative to the placebo group at 4 months of follow-up.

Conclusions

Doxycycline decreases the systemic inflammatory burden in patients with myocardial infarction and especially down-regulates MMP-7, MMP-8, and MMP-8/TIMP-1. Doxycycline might prevent or reduce the risk of secondary myocardial infarctions by providing a systemic anti-proteolytic and -inflammatory shield.
Literatur
1.
Zurück zum Zitat Sorsa T, Tjaderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 2006;38:306–21.PubMedCrossRef Sorsa T, Tjaderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 2006;38:306–21.PubMedCrossRef
2.
Zurück zum Zitat Tayebjee MH, Lip GY, MacFadyen RJ. Matrix metalloproteinases in coronary artery disease: clinical and therapeutic implications and pathological significance. Curr Med Chem. 2005;12:917–25.PubMedCrossRef Tayebjee MH, Lip GY, MacFadyen RJ. Matrix metalloproteinases in coronary artery disease: clinical and therapeutic implications and pathological significance. Curr Med Chem. 2005;12:917–25.PubMedCrossRef
3.
Zurück zum Zitat Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM, Powell JT. Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 1995;15:1145–51.PubMedCrossRef Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM, Powell JT. Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 1995;15:1145–51.PubMedCrossRef
4.
Zurück zum Zitat Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci. 1995;748:501–7.PubMedCrossRef Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci. 1995;748:501–7.PubMedCrossRef
5.
Zurück zum Zitat Johnson JL. Matrix metalloproteinases: influence on smooth muscle cells and atherosclerotic plaque stability. Expert Rev Cardiovasc Ther. 2007;5:265–82.PubMedCrossRef Johnson JL. Matrix metalloproteinases: influence on smooth muscle cells and atherosclerotic plaque stability. Expert Rev Cardiovasc Ther. 2007;5:265–82.PubMedCrossRef
6.
Zurück zum Zitat Lambert E, Dassé E, Haye B, Petitfrère E. TIMPs as multifacial proteins. Crit Rev Oncol Hematol. 2004;49:187–98.PubMedCrossRef Lambert E, Dassé E, Haye B, Petitfrère E. TIMPs as multifacial proteins. Crit Rev Oncol Hematol. 2004;49:187–98.PubMedCrossRef
7.
Zurück zum Zitat Visse Robert, Nagase Hideaki. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92:827–39.PubMedCrossRef Visse Robert, Nagase Hideaki. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92:827–39.PubMedCrossRef
8.
Zurück zum Zitat Qiang H, Zhou ZX, Ma AQ, Cheng H, Zhou P. Implications of serum matrix metalloproteinase-8 elevation in patients with acute coronary syndrome. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:831–3.PubMed Qiang H, Zhou ZX, Ma AQ, Cheng H, Zhou P. Implications of serum matrix metalloproteinase-8 elevation in patients with acute coronary syndrome. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:831–3.PubMed
9.
Zurück zum Zitat Tuomainen AM, Nyyssonen K, Laukkanen JA, Tervahartiala T, Tuomainen TP, Salonen JT, et al. Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men. Arterioscler Thromb Vasc Biol. 2007;27:2722–8.PubMedCrossRef Tuomainen AM, Nyyssonen K, Laukkanen JA, Tervahartiala T, Tuomainen TP, Salonen JT, et al. Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men. Arterioscler Thromb Vasc Biol. 2007;27:2722–8.PubMedCrossRef
10.
Zurück zum Zitat Herman MP, Sukhova GK, Libby P, Gerdes N, Tang N, Horton DB, et al. Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling. Circulation. 2001;104:1899–904.PubMedCrossRef Herman MP, Sukhova GK, Libby P, Gerdes N, Tang N, Horton DB, et al. Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling. Circulation. 2001;104:1899–904.PubMedCrossRef
11.
Zurück zum Zitat Turu MM, Krupinski J, Catena E, Rosell A, Montaner J, Rubio F, et al. Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound. Atherosclerosis. 2006;187:161–9.PubMedCrossRef Turu MM, Krupinski J, Catena E, Rosell A, Montaner J, Rubio F, et al. Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound. Atherosclerosis. 2006;187:161–9.PubMedCrossRef
12.
Zurück zum Zitat Smith FB, Fowkes FG, Rumley A, Lee AJ, Lowe GD, Hau CM. Tissue plasminogen activator and leucocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh artery study. Eur Heart J. 2000;21:1607–13.PubMedCrossRef Smith FB, Fowkes FG, Rumley A, Lee AJ, Lowe GD, Hau CM. Tissue plasminogen activator and leucocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh artery study. Eur Heart J. 2000;21:1607–13.PubMedCrossRef
13.
Zurück zum Zitat Jones CB, Sane DC, Herrington DM. Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res. 2003;59:812–23.PubMedCrossRef Jones CB, Sane DC, Herrington DM. Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res. 2003;59:812–23.PubMedCrossRef
14.
Zurück zum Zitat Halpert I, Sires UI, Roby JD, Potter-Perigo S, Wight TN, Shapiro SD. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA. 1996;93:9748–53.PubMedCentralPubMedCrossRef Halpert I, Sires UI, Roby JD, Potter-Perigo S, Wight TN, Shapiro SD. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA. 1996;93:9748–53.PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Münzel T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108:1440–5.PubMedCrossRef Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Münzel T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108:1440–5.PubMedCrossRef
16.
Zurück zum Zitat Karakas M, Koenig W, Zierer A, Herder C, Rottbauer W, Baumert J. Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study. J Intern Med. 2012;271:43–50.PubMedCrossRef Karakas M, Koenig W, Zierer A, Herder C, Rottbauer W, Baumert J. Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study. J Intern Med. 2012;271:43–50.PubMedCrossRef
17.
Zurück zum Zitat Saari H, Suomalainen K, Lindy O, Konttinen YT, Sorsa T. Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. Biochem Biophys Res Commun. 1990;171:979–87.PubMedCrossRef Saari H, Suomalainen K, Lindy O, Konttinen YT, Sorsa T. Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. Biochem Biophys Res Commun. 1990;171:979–87.PubMedCrossRef
18.
Zurück zum Zitat Wang Y, Rosen H, Madtes DK, Shao B, Martin TR, Heinecke JW, et al. Myeloperoxidase inactivates TIMP-1 by oxidizing its N-terminal cysteine residue: an oxidative mechanism for regulating proteolysis during inflammation. J Biol Chem. 2007;282:31826–34.PubMedCrossRef Wang Y, Rosen H, Madtes DK, Shao B, Martin TR, Heinecke JW, et al. Myeloperoxidase inactivates TIMP-1 by oxidizing its N-terminal cysteine residue: an oxidative mechanism for regulating proteolysis during inflammation. J Biol Chem. 2007;282:31826–34.PubMedCrossRef
19.
Zurück zum Zitat Fu X, Kassim SY, Parks WC, Heinecke JW. Hypochlorous acid generated by myeloperoxidase modifies adjacent tryptophan and glycine residues in the catalytic domain of matrix metalloproteinase-7 (matrilysin): an oxidative mechanism for restraining proteolytic activity during inflammation. J Biol Chem. 2003;278:28403–9.PubMedCrossRef Fu X, Kassim SY, Parks WC, Heinecke JW. Hypochlorous acid generated by myeloperoxidase modifies adjacent tryptophan and glycine residues in the catalytic domain of matrix metalloproteinase-7 (matrilysin): an oxidative mechanism for restraining proteolytic activity during inflammation. J Biol Chem. 2003;278:28403–9.PubMedCrossRef
20.
Zurück zum Zitat Kardara M, Papazafiropoulou A, Katsakiori P, Petropoulos C, Jelastopulu E. Protective effect of doxycycline use on coronary artery disease? J Infect. 2006;52:243–6.PubMedCrossRef Kardara M, Papazafiropoulou A, Katsakiori P, Petropoulos C, Jelastopulu E. Protective effect of doxycycline use on coronary artery disease? J Infect. 2006;52:243–6.PubMedCrossRef
21.
Zurück zum Zitat Lauhio A, Konttinen YT, Tschesche H, Nordström D, Salo T, Lähdevirta J, et al. Reduction of matrix metalloproteinase-8-neutrophil collagenase levels during long term doxycycline treatment of reactive arthritis. Antimicrob Agents Chemother. 1994;38:400–2.PubMedCentralPubMedCrossRef Lauhio A, Konttinen YT, Tschesche H, Nordström D, Salo T, Lähdevirta J, et al. Reduction of matrix metalloproteinase-8-neutrophil collagenase levels during long term doxycycline treatment of reactive arthritis. Antimicrob Agents Chemother. 1994;38:400–2.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent Res. 1998;12:12–26.PubMedCrossRef Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent Res. 1998;12:12–26.PubMedCrossRef
23.
Zurück zum Zitat Abdul-Hussien H, Hanemaaijer R, Verheijen JH, van Bockel JH, Geelkerken RH, Lindeman JH. Doxycycline therapy for abdominal aneurysm: improved proteolytic balance through reduced neutrophil content. J Vasc Surg. 2009;49:741–9.PubMedCrossRef Abdul-Hussien H, Hanemaaijer R, Verheijen JH, van Bockel JH, Geelkerken RH, Lindeman JH. Doxycycline therapy for abdominal aneurysm: improved proteolytic balance through reduced neutrophil content. J Vasc Surg. 2009;49:741–9.PubMedCrossRef
24.
Zurück zum Zitat Gu Y, Lee HM, Simon SR, Golub LM. Chemically modified tetracycline-3 (CMT-3): a novel inhibitor of the serine proteinase, elastase. Pharmacol Res. 2011;64:595–601.PubMedCrossRef Gu Y, Lee HM, Simon SR, Golub LM. Chemically modified tetracycline-3 (CMT-3): a novel inhibitor of the serine proteinase, elastase. Pharmacol Res. 2011;64:595–601.PubMedCrossRef
25.
Zurück zum Zitat Gu Y, Lee HM, Sorsa T, Salminen A, Ryan ME, Slepian MJ, et al. Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: a mechanistic link between local and systemic inflammation. Pharmacol Res. 2011;64:573–9.PubMedCrossRef Gu Y, Lee HM, Sorsa T, Salminen A, Ryan ME, Slepian MJ, et al. Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: a mechanistic link between local and systemic inflammation. Pharmacol Res. 2011;64:573–9.PubMedCrossRef
26.
Zurück zum Zitat Sinisalo J, Mattila K, Nieminen MS, Valtonen V, Syrjälä M, Sundberg S, Saikku P. The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production. J Antimicrob Chemother. 1998;41:85–92.PubMedCrossRef Sinisalo J, Mattila K, Nieminen MS, Valtonen V, Syrjälä M, Sundberg S, Saikku P. The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production. J Antimicrob Chemother. 1998;41:85–92.PubMedCrossRef
27.
Zurück zum Zitat Rautelin HI, Oksanen AM, Veijola LI, Sipponen P, Tervahartiala T, Sorsa T, et al. Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis. Ann Med. 2009;41:208–15.PubMedCrossRef Rautelin HI, Oksanen AM, Veijola LI, Sipponen P, Tervahartiala T, Sorsa T, et al. Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis. Ann Med. 2009;41:208–15.PubMedCrossRef
28.
Zurück zum Zitat Sorsa T, Tervahartiala T, Leppilahti J, Hernandez M, Gamonal J, Tuomainen AM, et al. Collagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases. Therapeutic response to non-antimicrobial properties of tetracyclines. Pharmacol Res. 2011;63:108–13.PubMedCrossRef Sorsa T, Tervahartiala T, Leppilahti J, Hernandez M, Gamonal J, Tuomainen AM, et al. Collagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases. Therapeutic response to non-antimicrobial properties of tetracyclines. Pharmacol Res. 2011;63:108–13.PubMedCrossRef
29.
Zurück zum Zitat Dollery CM, Owen CA, Sukhova GK, Krettek A, Shapiro SD, Libby P. Neutrophil elastase in human atherosclerotic plaques: production by macrophages by macrophages. Circulation. 2003;107:2829–36.PubMedCrossRef Dollery CM, Owen CA, Sukhova GK, Krettek A, Shapiro SD, Libby P. Neutrophil elastase in human atherosclerotic plaques: production by macrophages by macrophages. Circulation. 2003;107:2829–36.PubMedCrossRef
30.
Zurück zum Zitat Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev. 2005;85:1–31.PubMedCrossRef Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev. 2005;85:1–31.PubMedCrossRef
31.
Zurück zum Zitat Cheng C, Tempel D, van Haperen R, van Damme L, Algür M, Krams R, et al. Activation of MMP8 and MMP13 by angiotensin II correlates to severe intra-plaque hemorrhages and collagen breakdown in atherosclerotic lesions with a vulnerable phenotype. Atherosclerosis. 2009;204:26–33.PubMedCrossRef Cheng C, Tempel D, van Haperen R, van Damme L, Algür M, Krams R, et al. Activation of MMP8 and MMP13 by angiotensin II correlates to severe intra-plaque hemorrhages and collagen breakdown in atherosclerotic lesions with a vulnerable phenotype. Atherosclerosis. 2009;204:26–33.PubMedCrossRef
32.
Zurück zum Zitat Hästbacka J, Tiainen M, Hynninen M, Kolho E, Tervahartiala T, Sorsa T, et al. Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The association with therapeutic hypothermia. Resuscitation. 2012;83:197–201.PubMedCrossRef Hästbacka J, Tiainen M, Hynninen M, Kolho E, Tervahartiala T, Sorsa T, et al. Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The association with therapeutic hypothermia. Resuscitation. 2012;83:197–201.PubMedCrossRef
33.
Zurück zum Zitat van den Borne SW, Cleutjens JP, Hanemaaijer R, Creemers EE, Smits JF, Daemen MJ, et al. Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction. Cardiovasc Pathol. 2009;18:37–43.PubMedCrossRef van den Borne SW, Cleutjens JP, Hanemaaijer R, Creemers EE, Smits JF, Daemen MJ, et al. Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction. Cardiovasc Pathol. 2009;18:37–43.PubMedCrossRef
34.
Zurück zum Zitat Kato R, Momiyama Y, Ohmori R, Taniguchi H, Nakamura H, Ohsuzu F. Plasma matrix metalloproteinase-8 concentrations are associated with the presence and severity of coronary artery disease. Circ J. 2005;69:1035–40.PubMedCrossRef Kato R, Momiyama Y, Ohmori R, Taniguchi H, Nakamura H, Ohsuzu F. Plasma matrix metalloproteinase-8 concentrations are associated with the presence and severity of coronary artery disease. Circ J. 2005;69:1035–40.PubMedCrossRef
35.
Zurück zum Zitat Momiyama Y, Ohmori R, Tanaka N, Kato R, Taniguchi H, Adachi T, et al. High plasma levels of matrix metalloproteinase-8 in patients with unstable angina. Atherosclerosis. 2010;209:206–10.PubMedCrossRef Momiyama Y, Ohmori R, Tanaka N, Kato R, Taniguchi H, Adachi T, et al. High plasma levels of matrix metalloproteinase-8 in patients with unstable angina. Atherosclerosis. 2010;209:206–10.PubMedCrossRef
36.
Zurück zum Zitat Pussinen PJ, Sarna S, Puolakkainen M, Ohlin H, Sorsa T, Pesonen E. The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence. Int J Cardiol. 2012; doi:10.1016/j.ijcard.2011.12.095.PubMed Pussinen PJ, Sarna S, Puolakkainen M, Ohlin H, Sorsa T, Pesonen E. The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence. Int J Cardiol. 2012; doi:10.​1016/​j.​ijcard.​2011.​12.​095.PubMed
37.
Zurück zum Zitat Hanemaaijer R, Visser H, Koolwijk P, Sorsa T, Salo T, Golub LM, et al. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv Dent Res. 1998;12:114–8.PubMedCrossRef Hanemaaijer R, Visser H, Koolwijk P, Sorsa T, Salo T, Golub LM, et al. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv Dent Res. 1998;12:114–8.PubMedCrossRef
38.
Zurück zum Zitat García RA, Pantazatos DP, Gessner CR, Go KV, Woods VL Jr, Villarreal FJ. Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry. Mol Pharmacol. 2005;67:1128–36.PubMedCrossRef García RA, Pantazatos DP, Gessner CR, Go KV, Woods VL Jr, Villarreal FJ. Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry. Mol Pharmacol. 2005;67:1128–36.PubMedCrossRef
39.
Zurück zum Zitat Tuomainen AM, Kormi I, Havulinna AS, Tervahartiala T, Salomaa V, Sorsa T, et al. Serum tissue-degrading proteinases and incident cardiovascular disease events. Eur J Prev Cardiol. 2012; doi:10.1177/2047487312465524.PubMed Tuomainen AM, Kormi I, Havulinna AS, Tervahartiala T, Salomaa V, Sorsa T, et al. Serum tissue-degrading proteinases and incident cardiovascular disease events. Eur J Prev Cardiol. 2012; doi:10.​1177/​2047487312465524​.PubMed
40.
Zurück zum Zitat Payne JB, Golub LM, Stoner JA, Lee HM, Reinhardt RA, Sorsa T, et al. The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. J Am Dent Assoc. 2011;142:262–73.PubMedCentralPubMedCrossRef Payne JB, Golub LM, Stoner JA, Lee HM, Reinhardt RA, Sorsa T, et al. The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. J Am Dent Assoc. 2011;142:262–73.PubMedCentralPubMedCrossRef
Metadaten
Titel
The effect of prolonged systemic doxycycline therapy on serum tissue degrading proteinases in coronary bypass patients: a randomized, double-masked, placebo-controlled clinical trial
verfasst von
Immi Kormi
Hatem Alfakry
Taina Tervahartiala
Pirkko J. Pussinen
Juha Sinisalo
Timo Sorsa
Publikationsdatum
01.05.2014
Verlag
Springer Basel
Erschienen in
Inflammation Research / Ausgabe 5/2014
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-013-0704-2

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