The Relationship of Adiponectin in Adipose Tissue, Thy-1 in Plaques, and Inflammatory Mediators With Cardiac Diseases

The Relationship of Adiponectin in Adipose Tissue, Thy-1 in Plaques, and Inflammatory

Atherosclerosis is an inflammatory process in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial trees and is known as the main cause of coronary artery disease (CAD). Recently, there are more and more studies highlighted the potential importance of adipose tissue in relation to inflammation effects on CAD pathogenesis. However, it remains unclear whether Thy-1, adiponectin or any other inflammatory mediators in mediastinal adipose tissue contribute to CAD. In this study, we aim to analyze the expression of inflammatory mediators' expression via in vitro assay (3T3-L1 cell culture) and in vivo assay (human adipose tissues).

Study Overview

• Status: Completed
• Conditions: Heart Surgery
• Intervention / Treatment: Procedure: CAD; Procedure: VHD

Detailed Description

In addition, we'd like to investigate the association of the investigators' findings with clinical atherosclerotic risks, medications (statins or antiplatelet), and blood sugar. Now, we've established cell assay and successfully transformed mature adipocyte from 3T3-L1 cells. Besides, there were nighty-six patients enrolled into this study. Flow cytometry of Thy-1 and MCP-1 concentration in cultured medium by ELISA were also analyzed.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• coronary artery bypass grafting surgery
• valvular surgery

Exclusion Criteria:

• liver disease (GPT 2 times greater than normal limits)
• chronic renal insufficiency (Creatinine > 2.0 mg/dL)
• neoplastic diseases
• taking steroids
• congestive heart failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAD; Patients with valve diseases proposed to have cardiac operations will be enrolled in this study, but those with congestive heart failure are excluded. Besides, those patients with valve diseases should have patent coronary arteries on coronary angiography.	Procedure: CAD; Patients with CAD diseases proposed to have cardiac operations will be enrolled in this study, but those with congestive heart failure are excluded. Besides, those patients with valve diseases should have patent coronary arteries on coronary angiography.; Other Names: coronary artery disease
Experimental: VHD; Patients with valve diseases proposed to have cardiac operations will be enrolled in this study, but those with congestive heart failure are excluded. Besides, those patients with valve diseases should have patent coronary arteries on coronary angiography.	Procedure: VHD; Patients with valve diseases proposed to have cardiac operations will be enrolled in this study, but those with congestive heart failure are excluded. Besides, those patients with valve diseases should have patent coronary arteries on coronary angiography.; Other Names: valve diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CD91 (Thy-1)	up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
CD45	up to 24 months

Collaborators and Investigators

• Sponsor: Far Eastern Memorial Hospital

Publications and helpful links

General Publications

• Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999 Dec 21-28;100(25):2473-6. doi: 10.1161/01.cir.100.25.2473.
• Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O'Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003 Nov 18;108(20):2460-6. doi: 10.1161/01.CIR.0000099542.57313.C5. Epub 2003 Oct 27.
• Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002 Nov 26;106(22):2767-70. doi: 10.1161/01.cir.0000042707.50032.19.
• Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003 Jan 24;278(4):2461-8. doi: 10.1074/jbc.M209033200. Epub 2002 Nov 12.
• Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med. 2000 Oct 19;343(16):1139-47. doi: 10.1056/NEJM200010193431602.
• Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000 Apr 18;101(15):1767-72. doi: 10.1161/01.cir.101.15.1767.
• Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation. 2000 May 9;101(18):2149-53. doi: 10.1161/01.cir.101.18.2149.
• Shimokawa H, Ito A, Fukumoto Y, Kadokami T, Nakaike R, Sakata M, Takayanagi T, Egashira K, Takeshita A. Chronic treatment with interleukin-1 beta induces coronary intimal lesions and vasospastic responses in pigs in vivo. The role of platelet-derived growth factor. J Clin Invest. 1996 Feb 1;97(3):769-76. doi: 10.1172/JCI118476.
• Miyata K, Shimokawa H, Kandabashi T, Higo T, Morishige K, Eto Y, Egashira K, Kaibuchi K, Takeshita A. Rho-kinase is involved in macrophage-mediated formation of coronary vascular lesions in pigs in vivo. Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2351-8. doi: 10.1161/01.atv.20.11.2351.
• Prescott MF, McBride CK, Court M. Development of intimal lesions after leukocyte migration into the vascular wall. Am J Pathol. 1989 Nov;135(5):835-46.
• Staiger H, Tschritter O, Machann J, Thamer C, Fritsche A, Maerker E, Schick F, Haring HU, Stumvoll M. Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans. Obes Res. 2003 Mar;11(3):368-72. doi: 10.1038/oby.2003.48.
• Yatagai T, Nagasaka S, Taniguchi A, Fukushima M, Nakamura T, Kuroe A, Nakai Y, Ishibashi S. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism. 2003 Oct;52(10):1274-8. doi: 10.1016/s0026-0495(03)00195-1.
• Matsuzawa Y. Adipocytokines and metabolic syndrome. Semin Vasc Med. 2005 Feb;5(1):34-9. doi: 10.1055/s-2005-871744.
• Filippi E, Sentinelli F, Romeo S, Arca M, Berni A, Tiberti C, Verrienti A, Fanelli M, Fallarino M, Sorropago G, Baroni MG. The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age <or=50 years). J Mol Med (Berl). 2005 Sep;83(9):711-9. doi: 10.1007/s00109-005-0667-z. Epub 2005 May 5.
• Shimabukuro M, Higa N, Asahi T, Oshiro Y, Takasu N, Tagawa T, Ueda S, Shimomura I, Funahashi T, Matsuzawa Y. Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocrinol Metab. 2003 Jul;88(7):3236-40. doi: 10.1210/jc.2002-021883.
• Fernandez-Real JM, Lopez-Bermejo A, Casamitjana R, Ricart W. Novel interactions of adiponectin with the endocrine system and inflammatory parameters. J Clin Endocrinol Metab. 2003 Jun;88(6):2714-8. doi: 10.1210/jc.2002-021583.
• Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000 Sep 1;96(5):1723-32.
• Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001 Feb 27;103(8):1057-63. doi: 10.1161/01.cir.103.8.1057.
• Miyazaki T, Shimada K, Mokuno H, Daida H. Adipocyte derived plasma protein, adiponectin, is associated with smoking status in patients with coronary artery disease. Heart. 2003 Jun;89(6):663. doi: 10.1136/heart.89.6.663. No abstract available.
• Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerotic disease. Clin Chim Acta. 2004 Jun;344(1-2):1-12. doi: 10.1016/j.cccn.2004.02.020.
• Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, Kishida K, Komuro R, Ouchi N, Kihara S, Nagai R, Funahashi T, Matsuzawa Y. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002 Oct 4;277(40):37487-91. doi: 10.1074/jbc.M206083200. Epub 2002 Jul 22.
• Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y; Osaka CAD Study Group. Coronary artery disease. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):85-9. doi: 10.1161/01.atv.0000048856.22331.50.
• Kojima S, Funahashi T, Sakamoto T, Miyamoto S, Soejima H, Hokamaki J, Kajiwara I, Sugiyama S, Yoshimura M, Fujimoto K, Miyao Y, Suefuji H, Kitagawa A, Ouchi N, Kihara S, Matsuzawa Y, Ogawa H. The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction. Heart. 2003 Jun;89(6):667. doi: 10.1136/heart.89.6.667. No abstract available.
• Nakamura Y, Shimada K, Fukuda D, Shimada Y, Ehara S, Hirose M, Kataoka T, Kamimori K, Shimodozono S, Kobayashi Y, Yoshiyama M, Takeuchi K, Yoshikawa J. Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart. 2004 May;90(5):528-33. doi: 10.1136/hrt.2003.011114.
• Iwashima Y, Horio T, Suzuki Y, Kihara S, Rakugi H, Kangawa K, Funahashi T, Ogihara T, Kawano Y. Adiponectin and inflammatory markers in peripheral arterial occlusive disease. Atherosclerosis. 2006 Oct;188(2):384-90. doi: 10.1016/j.atherosclerosis.2005.10.039.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 2, 2015
• First Submitted That Met QC Criteria: August 6, 2015
• First Posted (Estimate): August 10, 2015

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: August 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: CAD; VHD; Thy-1
• Other Study ID Numbers: FEMH-96091