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1.  Endovascular retrieval of an irrigation cannula from the thoracic aorta following cardiac surgery: A case report 
•Endovascular techniques to retrieve intra-vascular foreign bodies are a necessary component of the Vascular surgeon’s skill set.•Endovascular retrieval of intravascular foreign bodies is minimally invasive, relatively simple, and carries minimal morbidity compared to conventional open surgical techniques.•It is important to have a working knowledge of techniques and instruments required for retrieval of intravascular foreign bodies.
Endovascular techniques to retrieve intravascular foreign bodies are a necessary component of the Vascular surgeon's skill set. We report the successful retrieval of an embolized irrigation cannula from the thoracic aorta following aortic valve replacement.
Presentation of case
The patient is an 81 year old male who underwent coronary artery bypass grafting and aortic valve replacement. Prior to closure, the aortotomy was irrigated with heparinized saline using a syringe with an olive tip irrigation cannula. When the syringe was handed back to the nursing staff, the tip was noted to be missing but could not be found. Prior to closure of the sternum, the field was searched again for the tip and thus the chest was closed. The missing instrument then prompted an intraoperative chest radiograph that demonstrated a metal irrigation cannula superimposed on the cardiac silhouette. Additionally, a transesophageal echocardiogram was performed, which demonstrated the irrigation cannula within the descending thoracic aorta. Right common femoral artery was accessed and a thoracic aortogram was performed demonstrating the cannula to be lodged in the descending thoracic aorta. Intravascular ultrasound (IVUS) was performed to exclude an aortic abnormality preventing the caudad migration of the cannula. No aortic pathology was identified. A tri-lobed snare was used to grasp the cannula at its tip and withdrawn into the right external iliac artery. The cannula was successfully removed through a transverse arteriotomy in the distal right external iliac artery. The patient's postoperative course was uneventful.
Endovascular retrieval of intravascular foreign bodies is minimally invasive, relatively simple, and carries minimal morbidity compared to conventional open surgical techniques. This unusual case demonstrates the importance of a working knowledge of techniques and instruments requisite for retrieval of intravascular foreign bodies
PMCID: PMC4643470  PMID: 26521199
Endovascular retrieval of foreign body; Irrigation cannula; Complications following cardiac surgery
2.  The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms 
Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology.
PMCID: PMC4463699  PMID: 25993294
DNA methylation; AAA; KLHL35; CNN2; SERPINB9; ADCY10P1; aortic aneurysm
3.  Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease 
PLoS ONE  2014;9(9):e107440.
Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.
PMCID: PMC4161424  PMID: 25210746
4.  Novel pathways in the pathobiology of human abdominal aortic aneurysms 
Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males > 65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs.
A custom-designed “AAA-chip” was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes.
Altogether 38 of the 43 genes on the “AAA-chip” showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings.
The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.
PMCID: PMC3782105  PMID: 22797469
gene expression; vascular biology; aorta; abdominal aortic aneurysm
5.  Role of Complement Cascade in Abdominal Aortic Aneurysms 
The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs).
Methods and Results
Results of a genome-wide microarray expression profiling revealed 3,274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for STAT5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues.
These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.
PMCID: PMC3712630  PMID: 21493888
Abdominal aortic aneurysm; complement cascade; genetic association study; STAT5; chromatin immunoprecipitation
6.  Malondialdehyde/Acetaldehyde Adduct (MAA) is the Dominant Epitope Following MDA Modification of Proteins in Atherosclerosis 
Free radical biology & medicine  2010;49(10):1480-1486.
Antibodies to malondialdehyde (MDA) modified macromolecules (adducts) have been detected in the serum of patients with atherosclerosis and correlate with the progression of this disease. However, the epitope and its formation have not been characterized. Studies have shown that excess MDA can be degraded to acetaldehyde which combines with proteins to from a stable dihydropyridine adduct. To investigate, mice were immunized with (MDA) adducts in the absence of adjuvant and showed an increase in antibodies to MDA adducts and the carrier protein as the concentration of MDA was increased. In fact, a number of the commercially available antibodies to MDA modified proteins were able to be inhibited by a chemical analogue hexyl-MAA. Also, MDA/MAA adducts were detected in the serum and aortic tissue of JCR diabetic/atherosclerotic rats. These studies determined that commercially available antibodies to MDA were shown to predominantly react with the MAA adduct and are present in the JCR model of atherosclerosis in both the serum and aortic tissue. Therefore, the immune response to MDA modified proteins is most likely to the dihydropyridine structure (predominant epitope in MAA), and suggests that MAA adducts may be playing a role in the development and/or progression of atherosclerosis.
PMCID: PMC2952714  PMID: 20696236
Atherosclerosis; modified proteins; acetaldehyde; malondialdehyde; autoantibodies; lipid peroxidation; JCR rats
7.  Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms 
BMC Physiology  2011;11:9.
The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.
We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).
Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.
PMCID: PMC3125234  PMID: 21627813

Results 1-7 (7)