Audrey Courtois

18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture

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 positive for 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 positive for 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.

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in men, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature, we examined human and animal in vivo and in vitro studies to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17β-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in men and women, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.

Multimodality imaging assessment of the deleterious role of the intraluminal thrombus on the growth of abdominal aortic aneurysm in a rat model.

AbstractObjectivesTo evaluate imaging changes occurring in a rat model of elastase-induced abdominal aortic aneurysm (AAA), with emphasis on the intraluminal thrombus (ILT) occurrence.MethodsThe post-induction growth of the AAA diameter was characterized using ultrasound in 22 rats. ILT was reported on 13 rats that underwent 14 magnetic resonance imaging (MRI) 2-18 days post-surgery, and on 10 rats that underwent 18 fluoro-deoxyglucose (FDG) positron emission tomography (PET)/microcomputed tomography examinations 2-27 days post-surgery. Logistic regressions were used to establish the evolution with time of AAA length, diameter, ILT thickness, volume, stratification, MRI and FDG PET signalling properties, and histological assessment of inflammatory infiltrates.ResultsAll of the following significantly increased with time post-induction (p < 0.001): AAA length, AAA diameter, ILT maximal thickness, ILT volume, ILT iron content and related MRI signalling changes, quantitative uptake on FDG PET, and the magnitude of inflammatory infiltrates on histology. However, the aneurysm growth peak followed occurrence of ILT approximately 6 days after elastase infusion.ConclusionOur model emphasizes that occurrence of ILT precedes AAA peak growth. Aneurysm growth is associated with increasing levels of iron, signalling properties changes in both MRI and FDG PET, relating to its biological activities.Key Points• ILT occurrence in AAA is associated with increasing FDG uptake and growth. • MRI signalling changes in ILT reflect activities such as haemorrhage and RBC trapping. • Monitoring ILT activities using MRI may require no exogenous contrast agent.

18F-FDG PET/CT in the Management of Aortitis.

Background Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall, resulting in potentially life-threatening vascular complications. Therefore, it is important to establish a diagnosis as early as possible. Patients and Methods During a 4-year period, 428 consecutive patients referred to our department for aortic diseases underwent FDG PET/CT examinations. Among these, 18 patients (4.2%) were suspected to have aortitis. All of them had an initial positive FDG PET/CT uptake occurring in the aorta and major branches as evaluated by visual analysis of images and assessed with the final diagnosis of aortitis. During follow-up, after surgery and/or upon immunosuppressive treatment, each of these patients underwent a second PET/CT that was compared with the initial evaluation. In all cases, normalization of FDG uptake was correlated with clinical improvement. Conclusions Our study aimed to illustrate the potential clinical value of functional monitoring with PET/CT in the management of aortitis. FDG PET/CT constitutes a valuable imaging modality to establish an early diagnosis, monitor disease progression and treatment, and evaluate vascular complication and relapse. We highlight the importance of an early detection of inflammatory large-vessel pathology, which may represent a major threat.

Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the evolution of chronic aortic dissections

AIMS Despite adequate medical management, dissection of the descending aorta (type B) may develop complications, including aneurysmal progression and eventually rupture. Partial false lumen thrombosis has been identified as a marker of adverse evolution in chronic dissection. The aim of this study was to test the ability of complementary information, provided by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and peripheral biomarkers, to add pathophysiological significance and a prognostic value to morphological data. METHODS AND RESULTS We explored serial aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23 patients with type B dissection to predict complications from initial data and to investigate potential associations with aneurysmal expansion during follow-up. Complications occurred in 17 patients. Acute initial characteristics associated with complications were male gender (P = 0.021), arterial hypertension (P = 0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During follow-up (mean 16.7 ± 8.0 months), aneurysmal expansion was associated with false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029), elevated plasma concentrations of biomarkers of platelets (P-selectin, P = 0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis (PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation and fibrinolysis were related to false channel morphology, suggesting that thrombus biological dynamics may drive progressive expansion of type B dissections. CONCLUSION Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and biomarkers of thrombus renewal and lysis.

Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA without FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+Pos) and at a paired distant negative site (A+Neg) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+Pos compared with A+Neg. Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+Neg and A+Pos compared with the AO. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.

A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms

Heterozygous mutations in the SMAD3 gene were recently described as the cause of a form of non-syndromic familial aortic thoracic aneurysm and dissection (FTAAD) transmitted as an autosomal dominant disorder and often associated with early-onset osteoarthritis. This new clinical entity, called aneurysms-osteoarthritis syndrome (AOS) or Loeys-Dietz syndrome 3 (LDS3), is characterized by aggressive arterial damages such as aneurysms, dissections and tortuosity throughout the arterial tree. We report, here, the case of a 45 year-old man presenting multiple visceral arteries and abdominal aortic aneurysms but without dissection of the thoracic aorta and without any sign of osteoarthritis. Exome-sequencing revealed a new frameshift heterozygous c.455delC (p.Pro152Hisfs*34) mutation in the SMAD3 gene. This deletion is located in the exon 3 coding for the linker region of the protein and causes a premature stop codon at positions 556-558 in the exon 4. The same mutation was found in the probands mother and sister who had open surgery for abdominal aortic aneurysm and in one of his children who was 5 year-old and did not present aneurysm yet.

Increased Metabolic Activity Highlighted by Positron Emission Tomography/Computed Tomography in the Wall of the Dissected Ascending Aorta in a Patient With Horton Disease

Horton disease or giant-cell arteritis (GCA) is a chronic systemic vasculitis involving typically medium and large arteries. Giant-cell arteritis is a panarteritis characterized by a granulomatous inflammation, with lymphocytes, macrophages, and multinucleated giant cells related to autoimmune T-cell reactivity.1 Compared with conventional imaging tools (ultrasound, computed tomography (CT), MRI, and contrast angiography) that provide anatomic and morphological information, recent available imaging techniques such as positron emission tomography (PET)/CT provide metabolic assessment of the arterial wall. During the early 2000s, Sakalihasan et al2 observed a close correlation between clinically unstable abdominal aortic aneurysms and increased uptake of 18F-fluoro-2-deoxy-d-glucose (FDG) in the aneurysmal wall. A few years later, Hautzel et al3 studied the assessment of giant-cell arteritis with PET/CT. We describe a case of Horton disease involving the thoracic aorta and complicated with acute aortic dissection in a woman with a previous diagnosis of thoracic aortic aneurysm. In July 2011, a 66-year-old woman was referred to a cardiology center for evaluation of a recent mild hypertension related to use of high doses of corticosteroids. In December 2010, she had developed severe headache, rapid loss of weight, and elevation of sedimentation rate as high as 120 mm. Horton disease was diagnosed in April 2011 on temporal artery biopsy. During the first cardiologic examination, …

Abdominal Aortic Aneurysm (AAA): Is There a Role for the Prevention and Therapy Using Antioxidants?

BACKGROUND Abdominal aortic aneurysm (AAA) is a degenerative disease that causes mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seem to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. OBJECTIVES Human studies confirmed that oxidative stress and endothelial dysfunction, an important source of ROS production, were well associated with AAA development. Reducing oxidative stress by antioxidants can therefore be a good strategy for limiting AAA development. The objective of the present study is to review literature data favoring or not such a hypothesis. There is currently no evidence showing that strategies using classical low molecular weight antioxidants (vitamins C and E, β- carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function and also their capacity to stimulate enzymatic antioxidants through activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. CONCLUSION Clinical studies are therefore urgently necessary to confirm the potential beneficial effect of polyphenols in preventing or limiting AAA.

IgG4-related disease causing rapid evolution of a severe aortic valvular stenosis

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recognized emerging entity characterized by chronic fibroinflammation that can affect every organ but rarely affects the cardiovascular system. We report a rare case of IgG4-RSD involving an aortic valve that resulted in rapid progression of an aortic valvular stenosis and was successfully treated by aortic valve replacement and corticosteroids.