References of "SAKALIHASAN, Natzi"
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See detailFamily Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liege AAA Family Study.
SAKALIHASAN, Natzi ULg; Defraigne, Jean-Olivier ULg; Kerstenne, Marie-Ange et al

in Annals of vascular surgery (2014), 28

BACKGROUND: The objectives were to answer the following questions using a well-characterized population in Liege, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive ... [more ▼]

BACKGROUND: The objectives were to answer the following questions using a well-characterized population in Liege, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive family history for AAA, 2) what is the prevalence of AAAs among relatives of AAA patients; and 3) do familial and sporadic AAA cases differ in clinical characteristics. METHODS AND RESULTS: Unrelated AAA patients diagnosed at the Cardiovascular Surgery Department, University Hospital of Liege, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. In the initial interview 62 (10%) of the 618 AAA patients reported a positive family history for AAA. We divided the 618 patients into two study groups: Group I: 296 AAA patients (268; 91% males) were followed up with computerized tomography combined with positron emission tomography, and Group II: 322 AAA patients (295; 92% males) whose families were invited to ultrasonography screening. Ultrasonography screening identified 24 new AAAs among 186 relatives (>/= 50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonography screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P<0.0001). CONCLUSIONS: The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis and provide rationale for targeted screening of relatives of AAA patients. [less ▲]

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See detailSurgical treatment of bicuspid aortic valve disease: Knowledge gaps and research perspectives.
Della Corte, Alessandro; Body, Simon C.; Booher, Anna M. et al

in The Journal of thoracic and cardiovascular surgery (2014)

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See detailMultifactorial Relationship Between 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography Signaling and Biomechanical Properties in Unruptured Aortic Aneurysms
NCHIMI LONGANG, Alain ULg; CHERAMY-BIEN, Jean-Paul ULg; Gasser, T. Christian et al

in Circulation. Cardiovascular imaging (2014), 7

BACKGROUND: -The relationship between biomechanical properties and biological activities in aortic aneurysms was investigated with finite element simulations (FES) and 18F-fluoro-deoxyglucose (18F-FDG ... [more ▼]

BACKGROUND: -The relationship between biomechanical properties and biological activities in aortic aneurysms was investigated with finite element simulations (FES) and 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography (PET). METHODS AND RESULTS: -The study included 53 patients (45 males) with aortic aneurysms, 47 infrarenal (AAA) and 6 thoracic (TAA), who had at least one 18F-FDG PET/computed tomography. Over a 30-month period, more clinical events occurred in patients with increased 18F-FDG uptake on their last examination than in those without (5/18 (28%) vs. 2/35 (6%); P=0.03). Wall stress and stress/strength index computed by FES and 18F-FDG uptake were evaluating a total of 68 examinations. 25 (38%) examinations demonstrated at least one aneurysm wall area of increased 18F-FDG uptake. The mean number of these areas per examination was 1.6 (18/11) in TAAs vs. 0.25 (14/57) in AAAs, while the mean number of increased uptake areas co-localizing with highest wall stress and stress/strength index areas was 0.55 (6/11) and 0.02 (1/57), respectively. Quantitatively, 18F-FDG PET uptake correlated positively with both wall stress and stress/strength index (P<0.05). 18F-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. CONCLUSIONS: -Increased 18F-FDG PET uptake in aortic aneurysms is strongly related to aneurysm location, wall stress as derived by FES and patient's risk factors such as acquired and inherited susceptibilities. [less ▲]

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See detailHigh Prevalence of Abdominal Aortic Aneurysm in Patients with Three-vessel Coronary Artery Disease.
Durieux, R.; VAN DAMME, Hendrik ULg; Labropoulos, N. et al

in European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (2014)

OBJECTIVES: Currently, the prevalence of abdominal aortic aneurysm (AAA) in patients with coronary artery disease (CAD) and the correlation between CAD severity and AAA prevalence are not clearly known ... [more ▼]

OBJECTIVES: Currently, the prevalence of abdominal aortic aneurysm (AAA) in patients with coronary artery disease (CAD) and the correlation between CAD severity and AAA prevalence are not clearly known. We conducted a prospective study to determine the prevalence of AAA in patients undergoing coronary angiography and to determine the risk factors and a coronary profile associated with AAA. METHODS: Over an 18-month period, abdominal aortic ultrasound was performed on 1,000 patients undergoing coronary angiography for suspected or known CAD, or prior to valve surgery. Clinical characteristics and coronary profile were collected from the patients. RESULTS: The overall number of previously repaired, already diagnosed, and new cases of AAA in the study population was 42, yielding a prevalence of 4.2%. Among the patients with newly detected AAAs, only two had an AAA diameter of >54 mm and were therefore treated surgically. In men aged >/=65 years, the prevalence reached 8.6%, while in men with three-vessel CAD it was 14.4%. Multivariate analysis showed that age >/=65 years (p = .003), male gender (p = .003), family history of AAA (p = .01), current smoking (p = .002), and three-vessel CAD (p < .001) were significantly associated with a higher prevalence of AAA. CONCLUSION: The prevalence of AAA was high in men aged >/=65 years and in those with three-vessel CAD regardless of age. While our findings do not prove the cost-effectiveness of screening for AAA in these high risk patients, they do support the usefulness of a quick ultrasound examination of the abdominal aorta during routine transthoracic echocardiography in such patients. [less ▲]

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See detailA Novel Strategy to Translate the Biomechanical Rupture Risk of Abdominal Aortic Aneurysms to their Equivalent Diameter Risk: Method and Retrospective Validation.
Gasser, T. C.; Nchimi, A.; Swedenborg, J. et al

in European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (2014)

OBJECTIVE: To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ... [more ▼]

OBJECTIVE: To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ruptured and non-ruptured aneurysms. METHODS: Biomechanical parameters of ruptured and non-ruptured AAAs were retrospectively evaluated in a multicenter study. General patient data and high resolution computer tomography angiography (CTA) images from 203 non-ruptured and 40 ruptured aneurysmal infrarenal aortas. Three-dimensional AAA geometries were semi-automatically derived from CTA images. Finite element (FE) models were used to predict peak wall stress (PWS) and peak wall rupture index (PWRI) according to the individual anatomy, gender, blood pressure, intra-luminal thrombus (ILT) morphology, and relative aneurysm expansion. Average PWS diameter and PWRI diameter responses were evaluated, which allowed for the PWS equivalent and PWRI equivalent diameters for any individual aneurysm to be defined. RESULTS: PWS increased linearly and PWRI exponentially with respect to maximum AAA diameter. A size-adjusted analysis showed that PWS equivalent and PWRI equivalent diameters were increased by 7.5 mm (p = .013) and 14.0 mm (p < .001) in ruptured cases when compared to non-ruptured controls, respectively. In non-ruptured cases the PWRI equivalent diameters were increased by 13.2 mm (p < .001) in females when compared with males. CONCLUSIONS: Biomechanical parameters like PWS and PWRI allow for a highly individualized analysis by integrating factors that influence the risk of AAA rupture like geometry (degree of asymmetry, ILT morphology, etc.) and patient characteristics (gender, family history, blood pressure, etc.). PWRI and the reported annual risk of rupture increase similarly with the diameter. PWRI equivalent diameter expresses the PWRI through the diameter of the average AAA that has the same PWRI, i.e. is at the same biomechanical risk of rupture. Consequently, PWRI equivalent diameter facilitates a straightforward interpretation of biomechanical analysis and connects to diameter-based guidelines for AAA repair indication. PWRI equivalent diameter reflects an additional diagnostic parameter that may provide more accurate clinical data for AAA repair indication. [less ▲]

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See detail18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture.
Courtois, Audrey ULg; Richelle, Betty ULg; Hustinx, Roland ULg et al

in Journal of Nuclear Medicine (The) (2013), 54

Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots of positive uptake of ... [more ▼]

Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots of positive uptake of 18F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the 18F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no 18F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. METHODS: Biopsies of the AAA wall were obtained from patients with no 18F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site of positive uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. RESULTS: The sites of the aneurysmal wall with a positive 18F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. CONCLUSION: Positive 18F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture. [less ▲]

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See detailNew Insights Into Aortic Diseases A Report From the Third International Meeting on Aortic Diseases (IMAD3)
KUIVANIEMI, Helena; SAKALIHASAN, Natzi ULg; LEDERLE, Franck et al

in AORTA (2013), 1

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See detailMultidimensional growth measurements of abdominal aortic aneurysms.
Martufi, Giampaolo; Auer, Martin; Roy, Joy et al

in Journal of vascular surgery (2013), 58(3), 748-55

BACKGROUND: Monitoring the expansion of abdominal aortic aneurysms (AAAs) is critical to avoid aneurysm rupture in surveillance programs, for instance. However, measuring the change of the maximum ... [more ▼]

BACKGROUND: Monitoring the expansion of abdominal aortic aneurysms (AAAs) is critical to avoid aneurysm rupture in surveillance programs, for instance. However, measuring the change of the maximum diameter over time can only provide limited information about AAA expansion. Specifically, regions of fast diameter growth may be missed, axial growth cannot be quantified, and shape changes of potential interest for decisions related to endovascular aneurysm repair cannot be captured. METHODS: This study used multiple centerline-based diameter measurements between the renal arteries and the aortic bifurcation to quantify AAA growth in 51 patients from computed tomography angiography (CTA) data. Criteria for inclusion were at least 1 year of patient follow-up and the availability of at least two sufficiently high-resolution CTA scans that allowed an accurate three-dimensional reconstruction. Consequently, 124 CTA scans were systematically analyzed by using A4clinics diagnostic software (VASCOPS GmbH, Graz, Austria), and aneurysm growth was monitored at 100 cross-sections perpendicular to the centerline. RESULTS: Monitoring diameter development over the entire aneurysm revealed the sites of the fastest diameter growth, quantified the axial growth, and showed the evolution of the neck morphology over time. Monitoring the development of an aneurysm's maximum diameter or its volume over time can assess the mean diameter growth (r = 0.69, r = 0.77) but not the maximum diameter growth (r = 0.43, r = 0.34). The diameter growth measured at the site of maximum expansion was ~16%/y, almost four times larger than the mean diameter expansion of 4.4%/y. The sites at which the maximum diameter growth was recorded did not coincide with the position of the maximum baseline diameter (rho = 0 .12; P = .31). The overall aneurysm sac length increased from 84 to 89 mm during the follow-up (P < .001), which relates to the median longitudinal growth of 3.5%/y. The neck length shortened, on average, by 6.2% per year and was accompanied by a slight increase in neck angulation. CONCLUSIONS: Neither maximum diameter nor volume measurements over time are able to measure the fastest diameter growth of the aneurysm sac. Consequently, expansion-related wall weakening might be inappropriately reflected by this type of surveillance data. In contrast, localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements over the entire aneurysm sac. This information might further reinforce the quality of aneurysm surveillance programs. [less ▲]

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See detailTraitement endovasculaire des dissections de l'aorte descendante (type B).
BRULS, Samuel ULg; VAN DAMME, Hendrik ULg; SAKALIHASAN, Natzi ULg et al

in Revue Médicale de Liège (2012), 67(9), 468-74

Aortic dissection is one of the most serious aortic diseases by its potential for rupture, but also for other complications, such as cerebral or splanchnic ischemia, which may be fatal. If open surgery is ... [more ▼]

Aortic dissection is one of the most serious aortic diseases by its potential for rupture, but also for other complications, such as cerebral or splanchnic ischemia, which may be fatal. If open surgery is the rule for lesions of the ascending aorta (type A), type B (not concerning the ascending aorta) is first a matter of medical treatment except when complications are present. In this case the placement of a stentgraft is a valuable alternative to open surgery. We report a patient presenting with a type B aortic dissection, characterized by rapid expansion and complicated by peri-aortic leakage, who was successfully treated by thoracic aortic stentgraft placement. This was done in a hybrid operating room associating the characteristics of a classical operating room for cardio-vascular surgery with those of an interventional radiology suite. [less ▲]

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See detailBiomechanical Rupture Risk Assessment in Patients with Abdominal Aortic Aneurysms: Introducing Rupture Risk Equivalent Diameter.
Roy, J; Swedenborg, J; SAKALIHASAN, Natzi ULg et al

in Arteriosclerosis, Thrombosis, and Vascular Biology (2012), 32(A103),

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See detailOn the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.
PINCEMAIL, Joël ULg; Defraigne, Jean-Olivier ULg; Cheramy-Bien, J. P. et al

in Redox Report : Communications in Free Radical Research (2012), 17(4), 139-44

BACKGROUND: Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few ... [more ▼]

BACKGROUND: Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. METHODS AND RESULTS: Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (</= 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, beta-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), alpha-tocopherol (P = 0.016) but not when corrected for cholesterol values, beta-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. CONCLUSION: The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression. [less ▲]

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See detailApolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.
Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar et al

in Journal of the American College of Cardiology (2012), 60(8), 722-9

OBJECTIVES: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. BACKGROUND ... [more ▼]

OBJECTIVES: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. BACKGROUND: It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. METHODS: The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). RESULTS: LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 x 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). CONCLUSIONS: LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. [less ▲]

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See detailIncreased oxidative stress status is associated with abdominal aortic aneurysm
PINCEMAIL, Joël ULg; Defraigne, Jean-Olivier ULg; Albert, Adelin ULg et al

in University of Ferrara (Ed.) Second Internaional conference on environmental stressors in biology and medicine (2011, October)

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See detailBM-573 INHIBITS THE EARLY ATHEROSCLEROTIC LESIONS IN APO-E DEFICIENT MICE BY BLOCKING TP RECEPTORS AND THROMBOXANE SYNTHASE
Cherdon, Céline ULg; Rolin, Stéphanie; Hanson, Julien ULg et al

in Congress of the International Society of Thrombosis and Hemostasis- 57th Annual SSC Meeting (2011, July)

Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2() have recently ... [more ▼]

Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2() have recently received a lot of attention. This study aimed to investigate the effect of a dual thromboxane synthase inhibitor and thromboxane receptor antagonist (BM-573) and ASA on lesion formation in apolipoprotein E-deficient mice. The combination of ASA and BM-573 was also studied. Plasma measurements demonstrated that the treatments did not affect body weight or plasma cholesterol levels. BM-573, but not ASA, significantly decreased atherogenic lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB(2) synthesis but only BM-573 and the combination therapy were able to decrease firstly, plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) and secondly, the expression of these proteins in the aortic root of Apo E. These results were confirmed in endothelial cell cultures derived from human saphenous vein endothelial cells (HSVECs). In these cells, BM-573 also prevented the increased mRNA expression of ICAM-1 and VCAM-1 induced by U-46619 and 8-iso-PGF(2(). Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient in delaying atherosclerosis in Apo E(-/-) mice than sole inhibition of TXA(2) formation. [less ▲]

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See detailBM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
Cherdon, Céline ULg; Rolin, Stephanie; Hanson, Julien ULg et al

in Prostaglandins & Other Lipid Mediators (2011)

Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2() have recently ... [more ▼]

Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2() have recently received a lot of attention. This study aimed to investigate the effect of a dual thromboxane synthase inhibitor and thromboxane receptor antagonist (BM-573) and ASA on lesion formation in apolipoprotein E-deficient mice. The combination of ASA and BM-573 was also studied. Plasma measurements demonstrated that the treatments did not affect body weight or plasma cholesterol levels. BM-573, but not ASA, significantly decreased atherogenic lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB(2) synthesis but only BM-573 and the combination therapy were able to decrease firstly, plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) and secondly, the expression of these proteins in the aortic root of Apo E. These results were confirmed in endothelial cell cultures derived from human saphenous vein endothelial cells (HSVECs). In these cells, BM-573 also prevented the increased mRNA expression of ICAM-1 and VCAM-1 induced by U-46619 and 8-iso-PGF(2(). Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient in delaying atherosclerosis in Apo E(-/-) mice than sole inhibition of TXA(2) formation. [less ▲]

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See detailAnalysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19.
Lillvis, J. H.; Kyo, Y.; Tromp, G. et al

in BMC Medical Genetics (2011), 12(1), 14

ABSTRACT: BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA ... [more ▼]

ABSTRACT: BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database. METHODS: Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22) were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. RESULTS: Several SNPs were nominally associated with AAA (p < 0.05). The SNPs with most significant p-values were located near the CCAAT enhancer binding protein (CEBPG), peptidase D (PEPD), and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP) database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. CONCLUSIONS: Association testing of the functional positional candidate genes on the AAA1 locus on chromosome 19q13 demonstrated nominal association in three genes. PEPD and CD22 were considered the most promising candidate genes for altering AAA risk, based on gene function, association evidence, gene expression, and protein expression. [less ▲]

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