Expression of Angiogenic Factors in Myocardial Tissue
Status: | Completed |
---|---|
Conditions: | Peripheral Vascular Disease, Cardiology |
Therapuetic Areas: | Cardiology / Vascular Diseases |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 4/21/2016 |
Start Date: | August 2009 |
End Date: | August 2011 |
IRB #14547: Expression of Angiogenic Factors in Myocardial Tissue in Diabetic and Non-diabetic Patients Undergoing Coronary Bypass Surgery
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).
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.
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.
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
We found this trial at
1
site
University of Virginia Health System UVA Health System includes a 604-bed hospital, level I trauma...
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