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The purpose of this study is to evaluate whether angiogenesis is decreased in diabetic patients with coronary artery disease compared to non-diabetics with coronary artery disease. The protein expression of angiogenic factors will be examined in atrial tissue prior to initiation of cardiopulmonary bypass in patients undergoing coronary bypass surgery.
The goal of this project is to evaluate the tissue levels of HIF-1, VEGF and angiostatin in diabetic and non-diabetic patients coming for on-pump coronary artery bypass graft (CABG).
Coronary artery disease and its complications are the leading cause of death in the western world. Diabetes mellitus (DM) is one of the major risk factors to develop coronary artery disease, myocardial infarction and post-infarction complication1-3. Furthermore, mortality from myocardial infarction is almost doubled in diabetic patients compared to non-diabetics4. Despite significant amount of research, the basis for these differences in outcome still remains unclear. The survival of myocardial tissue subjected to ischemia can be increased by the ability to promote growth of new blood vessels into ischemic areas, thus limiting regions of impairment and ultimately preserving myocardial function. Hypoxia inducible factor (HIF) -1 is a transcription factor that promotes the expression of several genes that confer protection against hypoxia/ischemia through angiogenesis, erythropoiesis, vasodilation, and altered glucose metabolism5,6. Our hypothesis is that angiogenesis may be impaired in diabetes mainly via decreased protein expression and activation of HIF-1 and its main downstream target vascular endothelial growth factor (VEGF), as well as the inhibitor angiogenesis factor, angiostatin7, in the heart. Therefore the purpose of this study is to examine whether the angiogenic process during coronary ischemia is influenced by diabetes. To address these questions, HIF-1, VEGF and angiostatin protein expression will be evaluated in atrial tissue obtained from patients with and without diabetes who will undergo coronary bypass surgery. In addition comparison between emergency and elective procedure will be performed in regard to HIF-1 and VEGF protein levels and correlation with chronic statin therapy will be performed.
During the cannulation process, prior to initiation of cardiopulmonary bypass (CPB) during heart surgery, a small piece of the right atrium is cut in order to insert a venous cannula into that chamber. The investigators intend to use this piece of tissue (that is routinely wasted) in our protein and histological analyses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CABG patients | atrial tissue samples from CABG patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atrial tissue sample | Other | atrial tissue sample from CABG patient |
|
| Measure | Description | Time Frame |
|---|---|---|
| tissue levels of HIF-1, VEGF and angiostatin | The investigators will evaluate tissue levels of HIF-1, VEGF and angiostatin in diabetic and non-diabetic patients coming for on-pump CABG. | initiation of CPB/ day 1 |
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Inclusion Criteria:
Exclusion Criteria:
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diabetic & non-diabetic CABG patients
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| Name | Affiliation | Role |
|---|---|---|
| Jacob Raphael, MD | UVA Anesthesiology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Virginia Health System | Charlottesville | Virginia | 22908 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15364810 | Background | Aguilar D, Solomon SD, Kober L, Rouleau JL, Skali H, McMurray JJ, Francis GS, Henis M, O'Connor CM, Diaz R, Belenkov YN, Varshavsky S, Leimberger JD, Velazquez EJ, Califf RM, Pfeffer MA. Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Circulation. 2004 Sep 21;110(12):1572-8. doi: 10.1161/01.CIR.0000142047.28024.F2. Epub 2004 Sep 13. | |
| 15047657 |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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During the cannulation process before the initiation of CPB(cardiopulmonary bypass) a small piece of right atrial tissue is cut in order to insert venous drainage cannula to the right atrium. This small piece of tissue is discarded and is not sent for pathology.
| Background |
| Zairis MN, Lyras AG, Makrygiannis SS, Psarogianni PK, Adamopoulou EN, Handanis SM, Papantonakos A, Argyrakis SK, Prekates AA, Foussas SG. Type 2 diabetes and intravenous thrombolysis outcome in the setting of ST elevation myocardial infarction. Diabetes Care. 2004 Apr;27(4):967-71. doi: 10.2337/diacare.27.4.967. |
| 17699010 | Background | Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, Antman EM. Diabetes and mortality following acute coronary syndromes. JAMA. 2007 Aug 15;298(7):765-75. doi: 10.1001/jama.298.7.765. |
| 2974889 | Background | Abbott RD, Donahue RP, Kannel WB, Wilson PW. The impact of diabetes on survival following myocardial infarction in men vs women. The Framingham Study. JAMA. 1988 Dec 16;260(23):3456-60. |
| 9523843 | Background | Semenza GL. Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. J Lab Clin Med. 1998 Mar;131(3):207-14. doi: 10.1016/s0022-2143(98)90091-9. No abstract available. |
| 8089148 | Background | Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994 Sep 23;269(38):23757-63. |
| 15136506 | Background | Weihrauch D, Lohr NL, Mraovic B, Ludwig LM, Chilian WM, Pagel PS, Warltier DC, Kersten JR. Chronic hyperglycemia attenuates coronary collateral development and impairs proliferative properties of myocardial interstitial fluid by production of angiostatin. Circulation. 2004 May 18;109(19):2343-8. doi: 10.1161/01.CIR.0000129225.67353.1F. Epub 2004 May 10. |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |