20 ans de recherche clinique et fondamentale dans la pathogénie des anévrysmes de l’aorte abdominale.

in Revue Médicale de Liège (2006)

Primary sarcoma of an abdominal aortic aneurysm

in Abdominal Imaging (2006), 31(1, Jan-Feb), 117-119

Primary tumors of the aorta are extremely rare and the diagnosis is made most often after surgery or autopsy. Because clinical symptoms of abdominal sarcoma are similar to those of occlusive or aneurysmal ... [more ▼]

Primary tumors of the aorta are extremely rare and the diagnosis is made most often after surgery or autopsy. Because clinical symptoms of abdominal sarcoma are similar to those of occlusive or aneurysmal disease, aortic sarcomas are frequently mistaken for these lesions. The imaging findings are frequently nonspecific and therefore do not allow a definitive preoperative diagnosis. We report a case of an epithelioid angiosarcoma in the vessel wall of an abdominal aortic aneurysm. [less ▲]

Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

in Journal of Vascular Surgery (2005), 41(6), 1036-1042

Background: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells ... [more ▼]

Background: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. Methods: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs;2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFBI(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms; in male subjects. Results: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P =.0047; rs2070584, P =.015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (x(2) p =.014 and empirical P =.009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 (P=.037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN (P =.0169) and TIMP3 (P =.0023) in cases with a family history of AAA. Conclusions: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase I (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA. [less ▲]

Evidence for HLA-DQA1 locus being associated with abdominal aortic aneurysms in the Belgian population

in Circulation (2005, April 12), 111(14), 219

Abdominal aortic aneurysm.

in Lancet (2005), 365(9470), 1577-89

Abdominal aortic aneurysms cause 1.3% of all deaths among men aged 65-85 years in developed countries. These aneurysms are typically asymptomatic until the catastrophic event of rupture. Repair of large ... [more ▼]

Abdominal aortic aneurysms cause 1.3% of all deaths among men aged 65-85 years in developed countries. These aneurysms are typically asymptomatic until the catastrophic event of rupture. Repair of large or symptomatic aneurysms by open surgery or endovascular repair is recommended, whereas repair of small abdominal aortic aneurysms does not provide a significant benefit. Abdominal aortic aneurysm is linked to the degradation of the elastic media of the atheromatous aorta. An inflammatory cell infiltrate, neovascularisation, and production and activation of various proteases and cytokines contribute to the development of this disorder, although the underlying mechanisms are unknown. In this Seminar, we aim to provide an updated review of the pathophysiology, current and new diagnostic procedures, assessment, and treatment of abdominal aortic aneurysm to provide family practitioners with a working knowledge of this disorder. [less ▲]

De l’observation clinique à l’étude génomique : contribution à la connaissance des mécanismes de formation et de rupture des anévrysmes de l’aorte abdominale.

Post doctoral thesis (2005)

Contribution of Pet Scanning to the Evaluation of Abdominal Aortic Aneurysm

in Seminars in Vascular Surgery (2004), 17(2), 144-53

The size of abdominal aortic aneurysms (AAA) is the most usual predictor of the risk for rupture. Because chronic metalloproteinases production and activation by inflammatory cells causes degradation of ... [more ▼]

The size of abdominal aortic aneurysms (AAA) is the most usual predictor of the risk for rupture. Because chronic metalloproteinases production and activation by inflammatory cells causes degradation of elastin and collagen in the aneurysmal wall, the detection of an increased metabolic process preceding fissuration and rupture could be a more sensitive predictor of rupture risk. We investigated the metabolic activity of the aneurysmal wall by whole-body positron emission tomography (PET) in 26 patients with a documented AAA (mean diameter 63 mm, extremes 45 mm and 78 mm). A positive (18)F-fluorodeoxyglucose ((18)F-FDG) uptake at the level of the AAA was observed in 38% of the cases (10 of 26 patients). Nine of these 10 patients required emergent or urgent aneurysmectomy for ruptured (n = 1), leaking (n = 1), rapidly expanding (n = 2), or painful (n = 5) aneurysms; the negative (18)F-FDG uptake patients had a more benign course. This preliminary study suggests a possible correlation between (18)F-FDG uptake by the aneurysm wall and the triggering of processes leading to rupture. The (18)F-FDG uptake in the aneurysm wall may correspond to the accumulation of inflammatory cells responsible for the production and activation of degrading enzymes. PET scan seems useful in high-risk patients. Positive PET imaging in these cases would help us to decide to proceed with surgery, despite factors favoring a surveillance strategy. [less ▲]

Effect of cardiac resynchronization therapy on functional mitral regurgitation in heart failure.

in American Journal of Cardiology (2004), 94(11), 1462-5

Cardiac resynchronization therapy (CRT) reduces functional mitral regurgitation (MR) at rest. This study assessed exercise-induced changes in MR in patients with heart failure who were helped by CRT. The ... [more ▼]

Cardiac resynchronization therapy (CRT) reduces functional mitral regurgitation (MR) at rest. This study assessed exercise-induced changes in MR in patients with heart failure who were helped by CRT. The determinants of these exercise-induced changes in MR were analyzed in asynchronous and resynchronized left ventricles. [less ▲]

Familial abdominal aortic aneurysms: collection of 233 multiplex families.

in Journal of Vascular Surgery (2003), 37(2), 340-5

OBJECTIVE: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the ... [more ▼]

OBJECTIVE: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. Subjects and Methods: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags). RESULTS: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively. CONCLUSION: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors. [less ▲]

Axillary artery injury secondary to anterior shoulder dislocation: report of two cases.

in Acta Chirurgica Belgica (2002), 102(3), 187-91

Vascular injuries secondary to isolated shoulder dislocation are rare. Unawareness for closed axillary artery trauma by many physicians treating shoulder dislocations, counts often for missed or delayed ... [more ▼]

Vascular injuries secondary to isolated shoulder dislocation are rare. Unawareness for closed axillary artery trauma by many physicians treating shoulder dislocations, counts often for missed or delayed diagnosis. The authors describe two cases that presented with an anterior shoulder dislocation, complicated by a disruption of the axillary artery with subsequent thrombosis. The various pathogenic mechanisms are discussed. The pathognomic triad consists of anterior shoulder dislocation, absent or diminished distal pulse and an axillary protruding hematoma. Prompt surgical arterial repair is mandatory. [less ▲]