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Publications (5)10.56 Total impact

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    ABSTRACT: Systemic inflammation and increased matrix metalloproteinase (MMP) cause elastin degradation leading to abdominal aortic aneurysm (AAA) expansion. Several prospective studies report that statin therapy can reduce AAA expansion through anti-inflammation. We hypothesize that monocyte activity plays a pivotal role in this AAA development and this study examines patient peripheral blood monocyte cell adhesion, transendothelial migration, and MMP concentrations between AAA and non-AAA patients. Peripheral blood was collected and monocytes isolated from control (n = 15) and AAA (n = 13) patients. Monocyte adhesion, transmigration, and permeability assays were assessed. Luminex assays determined MMP-9 and tissue inhibitor of metalloproteinase-4 (TIMP-4) concentrations from cell culture supernatant and patient serum. AAA patient monocytes showed increased adhesion to the endothelium relative fluorescence units (RFU, 0.33 ± 0.17) versus controls (RFU, 0.13 ± 0.04; P = 0.005). Monocyte transmigration was also increased in AAA patients (RFU, 0.33 ± 0.11) compared with controls (RFU, 0.25 ± 0.04, P = 0.01). Greater numbers of adhesive (R(2) = 0.66) and transmigratory (R(2) = 0.86) monocytes were directly proportional to the AAA diameter. Significantly higher serum levels of MMP-9 (2149.14 ± 947 pg/mL) were found in AAA patients compared with controls (1189.2 ± 293; P = 0.01). TIMP-4 concentrations were significantly lower in AAA patients (826.7 ± 100 pg/mL) compared with controls (1233 ± 222 pg/mL; P = 0.02). Cell culture supernatant concentrations of MMP and TIMP from cocultures were higher than monocyte-only cultures. Monocytes from AAA patients have greater adhesion and transmigration through the endothelium in vitro, leading to elevated MMP-9 levels and the appropriate decrease in TIMP-4 levels. The ability to modulate monocyte activity may lead to novel medical therapies to decrease AAA expansion.
    Journal of Surgical Research 03/2014; · 2.02 Impact Factor
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    ABSTRACT: An active abdominal aortic aneurysm (AAA) screening program at a regional Veterans Affairs (VA) health system identifies patients at risk for AAA. The purpose of this study is to evaluate unique risk factors associated with the AAA diagnosis upon AAA screening examination to identify the most at risk patients for AAA. Data were extracted from a regional VA health care system to identify patients who underwent AAA screening within a 3-year period. An aortic diameter ≥3.0 cm was defined as an AAA. Patient risk factors included age, body mass index, total cholesterol, estimated glomerular filtration rate (eGFR), statin use, and active smoking status; the presence of hypertension, diabetes, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), or peripheral vascular disease (PVD) was also evaluated. Risk factors were compared in a multivariate analysis between patients with AAA and patients with a normal aorta. A total of 6,142 patients (mean ± SD age: 72.7 ± 5.3 years) were screened for AAA between January 2007 and December 2009. A total of 469 patients (7.6%) with AAA were identified. The following risk factors were significantly associated with a diagnosis of AAA: age >75 years (39.6% vs. 28.9%; P < 0.001), prevalence of CAD (43.1% vs. 28.5%; P < 0.001), COPD (26% vs. 11.4%; P < 0.001), PVD (37.3% vs. 7.7%; P < 0.001), eGFR <60 mL/min (36.7% vs. 24.3%; P < 0.001), and current smoking (23.2% vs. 15.3%; P < 0.001). The risk factors significantly associated with normal aortic size were the presence of diabetes (18.6% vs. 27.4%; P < 0.001) and total cholesterol ≥200 mg/dL (10.4% vs. 15%; P = 0.04). The diagnosis of AAA in a large screening study is typically identified in patients who are at high risk for cardiovascular disease. The presence of diabetes is a major cardiovascular risk factor that is more associated with normal aorta when compared to patients with the AAA diagnosis. Total cholesterol ≥200 mg/dL was associated with decreased AAA risk, and renal insufficiency was associated with increased AAA risk.
    Annals of Vascular Surgery 11/2013; · 0.99 Impact Factor
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    ABSTRACT: BACKGROUND: Circulating progenitor cells are integral to vascular health and effectively predict vascular reactivity. CD34 is a known marker of circulating progenitor cells. Few studies have examined the role of CD34+ cells in abdominal aortic aneurysm (AAA) disease and peripheral vascular disease (PVD). The aim of this study was to compare the percentage of CD34+ cells between patients with AAA versus PVD. MATERIALS AND METHODS: We collected peripheral whole blood from AAA or PVD patients. The blood was stained with fluorescently labeled antibodies against CD34 or isotype controls. We collected data using a flow cytometer and analyzed them. We also recorded risk factors such as hypertension, diabetes, total cholesterol, serum white blood cells, serum creatinine, body mass index, blood pressure, statin use, current smoking status, coronary artery disease, cerebral vascular accident, and chronic obstructive pulmonary disease. RESULTS: We enrolled 24 patients in this study (AAA, n = 12; PVD, n = 12). The AAA patients had a greater percentage of CD34+ cells compared with PVD patients. (r = 0.84; P = 0.016). There were no significant risk factors differences between AAA and PVD patients. CONCLUSIONS: Based on CD34+ cell counts, AAA is a less severe vascular disease than PVD. Whether CD34+ cells can serve as a biomarker for risk stratification or a potential therapy warrants further study.
    Journal of Surgical Research 04/2013; · 2.02 Impact Factor
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    ABSTRACT: OBJECTIVE: In 2007, Medicare guidelines were established to identify persons at risk for the presence of an abdominal aortic aneurysm (AAA). The purpose of this study is to evaluate the 5-year outcomes of an AAA screening program in a regional Veterans Affairs (VA) health care system. METHODS: Data were extracted from a regional VA health care network identifying all veteran males 65 to 75 years of age who smoked at least 100 cigarettes during their lifetime. In 2007, an AAA screening mandate was implemented allowing patients meeting screening criteria to be evaluated for AAA as part of the patient's health maintenance. AAA is identified as an aortic diameter size of 3.0 cm or greater. Clinician adherence to screening protocols and referral to a vascular surgeon for aneurysms >5.5 cm were also evaluated. RESULTS: A total of 9751 patients (71.5 ± 5.6 standard deviation years of age) were screened for an AAA over a 5-year period from January 1, 2007 to December 31, 2011. A total of 698 aneurysms (7.1%) were found. Referrals to a vascular surgeon were made on 45 patients with aneurysms >5.5 cm. Over a 5-year period, a total of 2754 patients (28.2%) were inappropriately screened: 416 patients were under 65 years old, 2243 patients were over 75 years old, 36 patients were women, and 123 patients without aneurysms had multiple screenings. In 2007, during the first year of implementation, 39.2% of patients were inappropriately screened. Over the next 4 years, inappropriate screenings decreased with 33.7% in 2008, 28.6% in 2009, 17.7% in 2010, and 14.3% in 2011. CONCLUSIONS: A large AAA screening program at the VA detects more aneurysms, but at smaller diameters than that published in clinical trials. Over time, the number of inappropriate AAA screenings has continued to decrease, demonstrating greater awareness and application of the AAA screening guidelines by primary care providers. Developing surveillance guidelines for small and medium aneurysms is a potential area for future research.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 11/2012; · 3.52 Impact Factor
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    ABSTRACT: Statin therapy is used in the medical management of patients with peripheral vascular disease (PVD) and abdominal aortic aneurysm (AAA) for the pleiotropic and anti-inflammatory benefits. We hypothesize that the inflammatory mechanisms of monocyte-endothelial cell interactions in endothelial barrier dysfunction are more significant in patients with PVD compared with those with AAA. The purpose of this study was to assess patient peripheral blood monocyte adhesion molecules by flow cytometry and monocyte-induced endothelial barrier dysfunction by using an in vitro endothelial cell layer and electric cell-substrate impedance sensing (ECIS) system. Peripheral blood was collected from patients with either PVD (ankle-brachial index <0.9, toe-arm index <0.8, or required lower extremity vascular intervention) or AAA (aortic diameter >3.0cm). Monocytes were isolated from fresh whole blood using an accuspin-histopaque technique. The separated monocytes underwent flow cytometry analysis to evaluate the expression levels of the cell membrane adhesion molecules: CD18, CD11a/b/c, and very late antigen-4. Endothelial cell function was assessed by adding monocytes to an endothelial monolayer on ECIS arrays and coculturing overnight. Peak changes in transendothelial electrical resistance were measured and compared between patient groups. Twenty-eight monocyte samples were analyzed for adhesion molecules (PVD, 19 and AAA, 9) via flow cytometry, and 11 patients were evaluated for endothelial dysfunction (PVD, 7 and AAA, 4) via ECIS. There was no significant difference between risk factors among PVD and AAA patients except for age, where AAA patients were significantly older than PVD patients in both flow cytometry and ECIS groups (P=0.02 and 0.01, respectively). There were significantly higher levels of adhesion molecules CD11a, CD18, and CD11c (averaged mean fluorescent intensity P values: 0.047, 0.038, and 0.014, respectively) in PVD patients compared with AAA patients. No significant difference was found for CD11b and very late antigen-4 expression (P=0.21 and 0.15, respectively). There was significantly more monocyte-endothelial cell dysfunction in patients with PVD versus patients with AAA, with a maximal effect seen at 15h after monocyte addition (P=0.032). Patients with PVD have increased expression levels of certain monocyte adhesion molecules and greater monocyte-induced endothelial layer dysfunction compared with those with AAA. This may lead to other methods of targeted therapy to improve outcomes of these vascular patients.
    Journal of Surgical Research 07/2012; 177(2):373-81. · 2.02 Impact Factor