Comparative Genome-Wide Transcriptional Analysis of Bilateral Internal Mammary Arteries
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ABSTRACT: In Coronary Artery Bypass Grafting (CABG), the combined use of Left or Right Internal Mammary Artery (LIMA or RIMA) -collectively known as Bilateral IMAs (BIMAs)- provides a survival advantage over the LIMA alone. Several studies analyzed the gene expression in LIMAs and other conduits, however they either used a candidate gene approach or analyzed a small number of samples. Additionally, RIMA has never been analyzed compared to LIMA. Here we report a genome-wide transcriptional analysis of BIMA to investigate the expression profile of these conduits in patients undergoing CABG. Marginal differences were reported between LIMA and RIMA (p <0.05) using a linear model for microarray data. Ingenuity Pathway Assist (IPA) analysis found no consistent set of over-represented pathways and no trends in patterns of gene expression. As expected, in comparing the BIMAs to the aorta, we found differences in pathways and processes associated with atherosclerosis, inflammation, and cell signaling. Although evidence in favor of the use of BIMA in CABG has been available for over a decade, their routine use in clinical practice remains very low accounting for only 4% of CABG procedures in the US. Despite differences in embryologic development, our genome-wide transcriptional analysis, show marginal differences between LIMA and RIMA. Taken together, clinical and genomic analyses provide evidences that could impact the independent or combined use of the BIMAs as a conduit in CABG.
Project description:In Coronary Artery Bypass Grafting (CABG), the combined use of Left or Right Internal Mammary Artery (LIMA or RIMA) -collectively known as Bilateral IMAs (BIMAs)- provides a survival advantage over the LIMA alone. Several studies analyzed the gene expression in LIMAs and other conduits, however they either used a candidate gene approach or analyzed a small number of samples. Additionally, RIMA has never been analyzed compared to LIMA. Here we report a genome-wide transcriptional analysis of BIMA to investigate the expression profile of these conduits in patients undergoing CABG. Marginal differences were reported between LIMA and RIMA (p <0.05) using a linear model for microarray data. Ingenuity Pathway Assist (IPA) analysis found no consistent set of over-represented pathways and no trends in patterns of gene expression. As expected, in comparing the BIMAs to the aorta, we found differences in pathways and processes associated with atherosclerosis, inflammation, and cell signaling. Although evidence in favor of the use of BIMA in CABG has been available for over a decade, their routine use in clinical practice remains very low accounting for only 4% of CABG procedures in the US. Despite differences in embryologic development, our genome-wide transcriptional analysis, show marginal differences between LIMA and RIMA. Taken together, clinical and genomic analyses provide evidences that could impact the independent or combined use of the BIMAs as a conduit in CABG. We selected 32 patients from whom we had frozen archival tissue from aorta, LIMA, and RIMA in the Cardiovascular Blood and Tissue Bank at the Valley Columbia Heart Center . The mammary and aortic tissues were harvested at time of CABG. The surgeon dissected the two most distal aspects of LIMA and RIMA segments and obtained a M-bM-^IM-%1cm sample for the tissue bank. The tissue sample was placed in a cryomold and processed as a M-bM-^@M-^\frozen sectionM-bM-^@M-^] specimen using standard OCT gel. Total RNA was extracted using Qiagen RNeasy Mini Kit, RNA integrity was assessed using the Agilent 2100 BioAnalyzer and RNA quantities and purity were determined using a NanoDrop Spectrophotometer. RNA samples were amplified using the NuGen Ovation RNA Amplification SystemM-BM- V2 The resulting cDNA was labeled and hybridized to the Affymetrix U133A 2.0 GeneChip. 73 arrays at the end.
Project description:Anesthetic gases elicit organ protection in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed at identifying myocardial transcriptional phenotypes and anesthetic-induced changes in gene expression to predict cardiovascular biomarkers and cardiac function after off-pump CABG. Keywords: cardiac surgery, anesthetics
Project description:Anesthetic gases elicit organ protection in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed at identifying myocardial transcriptional phenotypes and anesthetic-induced changes in gene expression to predict cardiovascular biomarkers and cardiac function after off-pump CABG. Experiment Overall Design: Patients scheduled for off-pump CABG were randomized into a group with the anesthetic gas sevoflurane (n=10) or the intravenous anesthetic propofol (n=10). Atrial samples were collected at the beginning and end of bypass surgery to determine gene expression profiles.
Project description:Pericardial sac surrounding the heart contains pericardial fluid (PF), which is rich in exosomes. PF exosomes increase angiogenesis in hypoxic endothelial cells and in animal model of hindlimb ischemia by passing the proangiogenic miRNAs to recipient cells. However, under pathological conditions such as diabetes, exosome cargo composition changes and harmful miRNAs can be transferred to the recipient cells and induce more deleterious effects in target tissues. In order to check cargo composition of different PF exosomes, we used PF exosomes from non-diabetic aortic valve replacement (AVR), mitral valve replacement (MVR), coronary artery bypass grafting (CABG) patients and CABG patients with diabetes.
Project description:MiRNA regulate the maintenance, differentiation and function of stem cells and progenitor cells. miRNA expression of progenitor cells located in the adventital layer of arterial vessels has not been characterized in either animal or human models. Further it is unknown if local arterial miRNA expression profiles change after injury of end organs supplied blood by these arterial conduits. CD34+/CD105- cells were extracted and analyzed for changes in miRNA expression after kidney specific ischemic injury. CD34+/CD105- cells were isolated from mouse renal artery after microvascular clamping of renal arteries bilaterally
Project description:The long-term survival of coronary artery bypass grafting (CABG) surgery depends on the patency of the grafts. A key problem is the lower patency of the saphenous vein (SV) compared to the arterial grafts such as internal thoracic artery (ITA) with unclear reasons despite of previous efforts to reveal them. We hypothesized that the intrinsic differences between the ITA and SV may involve the differences in post-translational modification (PTM) of proteins in these two types of vascular grafts. Hence, we applied PTM proteomics to uncover differences between ITA and SV, and to reveal a novel mechanism for the differences in long-term patency.
Project description:Postoperative atrial fibrillation (POAF) is a common complication in coronary artery bypass grafting (CABG). We investigated pre-existing biological derangements before CABG to provide molecular insights into the pathogenesis. Preoperative plasma samples of discovery set from matched cohorts in sinus rhythm and POAF respectively were analyzed using proteomic approaches to identify the differential proteins that were validated in a new cohort by ELISA. Bioinformatics analysis were performed to reveal the underlying mechanism of the onset of POAF. The results revealed that preoperative alteration of PPAR-alpha increased the susceptibility of POAF after CABG.
Project description:[original title] Gene expression response to the implantation of drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries. Different clinical outcomes have been observed for paclitaxel-eluting and bare metal cardiovascular stents. The aim of this project was to identify genes that might be associated with the observed clinical outcomes. Human left internal mammary artery (LIMA) was divided into three segments and and two of the segments were fitted with either a paclitaxel-eluting stent or a bare metal stent. The experiment includes three groups: control, paclitaxel-eluting stent, and bare metal stent, respectively. Each group includes four biological replicates (patients 1, 2, 4 and 5).
Project description:MiRNA regulate the maintenance, differentiation and function of stem cells and progenitor cells. miRNA expression of progenitor cells located in the adventital layer of arterial vessels has not been characterized in either animal or human models. Further it is unknown if local arterial miRNA expression profiles change after injury of end organs supplied blood by these arterial conduits. CD34+/CD105- cells were extracted and analyzed for changes in miRNA expression after kidney specific ischemic injury. CD34+/CD105- cells were isolated from renal artery after short warm ischemic time in living donor kidney explants and long warm ischemic time following radical nephrectomy for renal cell cancer
Project description:Transcriptional study to investigate differences in prefrontal cortex and striatum of mice that consumed ethanol despite negative consequences, which resembles the compulsive aspect of alcohol addiction. The transcriptional analysis performed in the striatum and prefrontal cortex revealed genes and biological pathways differentially regulated specifically in animals of the group Inflexible Drinkers that could be involved with the loss of control over voluntary ethanol consumption (da Silva E Silva et al., 2016; de Paiva Lima et al., 2017).