Expression of Angiogenic Factors in Myocardial Tissue

Completed

• Conditions: Coronary Artery Disease
• Interventions: Other: atrial tissue sample

• Registration Number: NCT01414621
• Lead Sponsor: University of Virginia

Brief Summary

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).

Detailed Description

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.

Study Timeline

• Study Start: 2009-08
• Study First Submitted: 2010-09-17
• Primary Completion: 2011-07
• Study Completion: 2011-08
• Study First Submitted QC: 2011-08-10
• Study First Posted: 2011-08-11
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-07
• Last Update Posted: 2016-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. on-pump CABG
2. 18 years of age & older
3. informed consent

Exclusion Criteria

1. active malignancy
2. severe lung disease (requiring home O2 therapy)
3. severe anemia<8g/dl
4. patient with moderate or severe renal dysfunction
5. off- pump CABG

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CABG patients	atrial tissue sample	atrial tissue samples from CABG patients

Primary Outcome Measures

Name	Time	Method
tissue levels of HIF-1, VEGF and angiostatin	initiation of CPB/ day 1	The investigators will evaluate tissue levels of HIF-1, VEGF and angiostatin in diabetic and non-diabetic patients coming for on-pump CABG.

Trial Locations

Locations (1)

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States