Published online before print February 21, 2008, doi: 10.1161/ATVBAHA.107.158576
© 2008 American Heart Association, Inc.
Clinical and Population Studies |
Dilation-Dependent Activation of Platelets and Prothrombin in Human Thoracic Ascending Aortic Aneurysm
From INSERM (Z.T., L.L., V.O., M.J.-P., J.-B.M., G.J.), U698, University Paris 7, Paris, France; AP-HP (L.L., P.N., U.H., J.-B.M., G.J.) Medical and Surgical Cardiology Department, Bichat Hospital, AP-HP, Paris, France, University Paris VII Denis Diderot (Z.T., L.L., P.N., J.L., J.-B.M., G.J.), and the Centre de reference Marfan et syndromes apparentes (G.J.), Bichat Hospital, AP-HP, Paris, France.
Correspondence to Pr Guillaume Jondeau, CHU Bichat, INSERM U698, 46, rue Henri Huchard, 75018 Paris, France. E-mail guillaume. jondeau{at}bch.aphp.fr
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Objectives— The purpose of this study was to investigate whether thoracic ascending aortic aneurysm (TAAA) induces platelet activation as mural thrombus participates in aortic dilatation in abdominal aortic aneurysm and TAAA are associated with rheological factors favoring coagulation activation.
Methods and Results— We studied the relation between coagulation activation and aortic diameter in Marfan patients (MFS) with various aortic diameters (n=52). We then studied patients presenting large aneurysms associated with bicuspid aortic valve (BAV) and degenerative form. Lastly, we used immunochemistry and biochemistry to investigate prothrombin/thrombin retention within the aortic wall. Microparticles, sGPV, tissue factor, and TAT complexes were increased in plasma from MFS with large aneurysms (
45 mm) compared to MFS with limited aortic dilatation (<45 mm). Similar elevations were observed in all patients with large aortic aneurysms, regardless of the etiology, the site of maximal aortic dilation, associated valvulopathy, risk factors, or treatments. P-selectin and platelet-bound fibrinogen were also increased, demonstrating platelet activation in large aneurysms. Significant increase in sCD146 plasma concentration suggested alteration of endothelium.
Conclusions— Platelet activation occurs in patients with large aneurysms of the ascending aorta, is dependent on aortic dilation, and is associated with thrombin generation, part of which appears to be retained in mucoid degeneration areas.
Platelet activation and thrombin formation were evidenced in Marfan patients with ascending aortic dilatation above 45 mm (but not below 45 mm), and in patients with large aneurysm of other aetiologies. Thrombin (susceptible to activate MMPs) present within the aortic wall suggests that it could participate in aortic dilatation.
Key Words: thoracic aortic aneurysm • coagulation • Marfan • platelets
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Thoracic ascending aortic aneurysms (TAAA) are defined by an enlargement of the ascending aorta. TAAA can be observed in old patients without clear etiologic factors, in whom it represents a primary degenerative pathology of the ascending aorta.1 But it can also occur in the younger population; it is then usually linked to a genetic or congenital disease. Marfan syndrome represents the majority of these cases. This is usually related to mutations in fibrillin12 and rarely to mutations in transforming growth factor (TGF)βR2, which can also be responsible for Loeys-Dietz Syndrome and familial aortic aneurysm.3–5 Other molecular abnormalities have been implicated, such as mutations in myosin,6 TGFβR1,5 ACTA2,7 or other currently unknown genes.8 Moreover, bicuspid aortic valves (BAV), which may be familial,9 are associated with a high risk of aneurysm of the ascending aorta.10
In contrast to their etiologic diversity, all localized aortic dilations share common rheological characteristics. In normal human aorta, the regular geometry (tubular shape and parallel walls) results in laminar blood flow and in a homogeneous shear rate, maintaining a physiological steady-state among the blood components and between the circulating blood and arterial wall.11 Changes in arterial geometry considerably modify rheological parameters and therefore influence interactions between blood components.11,12 The modulations by shear stress of platelet interactions with von Willebrand factor (vWF) exemplify the role of rheology in hemostasis.13,14 In this respect, an aneurysm of the ascending aorta induces rheological perturbations, characterized by vortices (low wall shear rate).15
Rheological disturbances have been suggested to play a role in mural thrombus formation associated with cerebral artery and abdominal aortic aneurysms, and the luminal thrombus appears to play a role in the progression of aortic dilation.16 In contrast with this localization, TAAAs are characterized by the absence of any mural thrombus formation1 (Figure 1) even in older patients with diffuse atherosclerosis. Therefore, TAAA offers a unique opportunity to test the hypothesis that platelets and the coagulation cascade could be activated by dilation of the ascending aorta, and could be associated with this pathology independently of a mural thrombus formation. There have been no clinical studies focusing on the hemostasis cascade in patients with TAAA. For this purpose, we explored markers of activation of both platelets and prothrombin in patients with TAAA. In a first step, we compared Marfan patients with various aortic diameters and matched controls. In a second step, we studied platelets and prothrombin activation in patients presenting TAAA of other aetiologies (BAV and degenerative).
|
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Population
One hundred fifty-six patients were divided into 4 groups (Table 1): Healthy individuals (Controls, n=66); Patients fulfilling international criteria for Marfan syndrome (MFS).17,18 They were subdivided into 2 groups: MFS patients with limited dilation (maximal aortic diameter <45 mm) (n=28), and MFS patients with large aneurysm19 (aortic diameter
45 mm) (n=24); TAAA patients scheduled for surgery because of aortic dilatation. Here, large aneurysms were associated with bicuspid aortic valves (BAV) (n=15), or were isolated with no sign of genetic disease (Degenerative; n=23). For more details, please see the supplemental data section, available online at http://atvb.ahajournals.org.
|
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Patient Groups
Clinical and echocardiographic data are summarized in Table 1. MFS patients were significantly younger (P<0.01) than those of the BAV and degenerative groups. Patients from the degenerative group were the oldest with, as expected, more cardiovascular risk factors (
2=10.5, P<0.01), mainly hypertension, a higher frequency of medications, and a higher incidence of significant aortic valve regurgitation (P<0.01).
Aortic valve stenosis was present more frequently in the BAV group (2=7.8, P<0.01). In this group, maximal aortic dilation was observed above the sinotubular junction (2=20, P<0.0001), whereas it was maximal at the level of the Valsalva sinuses in MFS patients, and the patients with degenerative aortic aneurysm.
Marfan and Controls: Relation of Platelet Activation to Aortic Diameter
No increase in plasma markers of platelet activation was observed in the group of MFS with limited dilatation (ie, maximal diameter <45 mm), when compared to age- and sex-matched control: microparticle count (Annexin-V positive) and concentrations of sGPV, Tissue factor and TAT were similar in the 2 groups (Table 2). In contrast, all these markers were significantly higher in plasma from MFS patients with large aneurysms (45 mm) (Table 2). The increase in microparticle concentration (Figure 1) was correlated to aortic diameter (P<0.05, r2=0.38) in the Marfan group with and without large aneurysms. Similar results were found for sGPV concentration (P<0.001, r2=0.56), and these 2 markers of platelet activation were highly correlated in the whole Marfan group (P<0.0001, r2=0.65).
|
Extension to Other Aetiologies of TAAA
Microparticles
Microparticle counts were increased in plasma of patients with large aneurysms of all etiologies (Marfan, BAV-associated or degenerative) when compared to controls (P<0.0001) (Table 2). However, plasma levels of microparticles were similar, regardless of etiology (Table 2) of large aneurysms. 93.2±3.9% of microparticles were positive for CD41 antibody (integrin GPIIb/IIIa) in patients with large aneurysms and 90.9±6.4 in controls (NS) demonstrating their platelet origin in both cases.
Plasma Markers
Other markers for platelet activation (sGPV, sCD40L) were also significantly (P<0.0001) higher in plasma of patients with large aneurysms than in that from controls, with no difference between etiologies (Table 2). In contrast, the plasma concentration of sP-selectin was not increased in association with large aneurysms compared to controls (36.2±1.7 ng/mL versus 34.2±1.8, ns).
We observed no difference in these plasma markers when patients were under low doses of aspirin. Aspirin blocks thromboxane A2 synthesis and platelet recruitment by this secreted TxA2. It thus limits the secondary progression of platelet activation, but does not block primary platelet activation.20
Platelet Markers
Platelet membrane expression of P-selectin, measured with FACs on whole blood, was low, but significantly higher in large aneurysms compared to controls (4.08±0.53% positive versus 2.91±0.56% in controls, P<0.05). Similar but more significant results were obtained by analyzing the curve shift induced by the specific antibody as compared to a nonrelevant antibody (Overton method) (large aneurysms versus controls: 14.6±2.1% versus 7.8±0.6%, P<0.01) (Figure 1A and 1B). P-selectin expression on platelets did not differ with regard to etiology.
Conversely, platelet-bound fibrinogen was not significantly different in large aneurysm patients compared to controls when measured by the classical analysis method (0.96±0.29% versus 0.89±0.21%, ns). However, curve shift analysis (Overton) revealed a small significant shift of the signal to the right in platelets originating from patients with large aneurysms (TAAA: 7.34±1.3% versus controls: 3.9±0.5%, P<0.05, Figure 1B).
Markers of Prothrombin Activation
In plasma of patients with large aneurysms, TF antigen concentration was significantly higher than in control plasma, regardless of etiology (Table 2). The 1-step recalcification clotting time was reduced for plasma of patients with large aneurysms compared to controls (175.8±8.0 seconds versus 210.7±7.9 seconds, P<0.001; Figure 2). The involvement of TF activity in the shortening of the clotting time was demonstrated by adding a blocking anti-TF antibody that prolonged the clotting time of patients with large aneurysms by 35.9±5.8%, to reach a value similar to that of controls. Plasma thrombin generation, measured using a global assay, showed an increased "endogenous thrombin potential" (ETP) for large aneurysms relative to controls (1902.3±74 nM.min–1 for TAAA versus 1712.8±63.7 nM.min–1 for controls, P<0.05; Figure 2) and an increased maximal thrombin generation (peak height) for the large aneurysm group (335.3±13.2 nmol/L versus 284.5±10.6 nmol/L for controls, P<0.001; Figure 2). Interestingly, there was a significant correlation between sGPV and maximal thrombin generation (r2=0.49, P<0.01) in plasma of patients with large aneurysms. Furthermore, TAT complexes were also slightly but significantly increased in the plasma of patients with large aneurysms (P<0.001, Table 2). These results were statistically similar for all aetiologies.
|
Endothelial Plasma Markers
Soluble vascular cell adhesion molecule (VCAM)-1 was not statistically different in large aneurysm and control groups (377.6±48.4 ng/mL versus 293.3±36.1 ng/mL, P=0.08). In contrast, sCD146 plasma levels were significantly higher in patients with large aneurysm than in controls, with no significant differences whatever the etiology of the TAAA (Table 2).
Inflammatory Markers
Fibrinogen and hsCRP levels were similar in large aneurysm patients and controls (2.8±0.1 g/L versus 2.6±0.2 g/L and 1.88±0.3 mg/L versus 1.47±0.2 mg/L, respectively). These markers were slightly, but not significantly, superior in degenerative group. This is consistent with greater age and the presence of more risk factors in this group.
Aortic Tissue Samples and Conditioned Media
In control aortic tissue, immunoreactivity for prothrombin/thrombin (II/IIa) was negative (Figure 3A). In contrast, aortic sections from patients with surgically removed large aneurysms, whatever the etiology, showed prominent immunoreactivity for factor II and IIa in the mucoid areas, which were localized in serial sections stained with Alcian blue (Figure 3A). These results were confirmed on conditioned media of aortic samples, where factor II and IIa were detected by immunoblotting (Figure 3B). Conditioned media from large aneurysms expressed larger bands of prothrombin and thrombin than conditioned media from controls. By ELISA, a higher concentration of TAT was detected in conditioned media of large aneurysms, regardless the etiology as compared to controls, supporting the immunohistological and immunoblot data (Figure 3C).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Our main result is the presence of biological signs of in vivo activation of both platelets and prothrombin in patients with thoracic ascending aortic aneurysm. This activation is only present when maximal aortic diameter is greater than 45 mm in Marfan patients of young age, devoid or risk factors, but not observed in MFS patients when maximal aortic diameter is less than 45 mm. It is also present in patients presenting large aneurysms of other aetiologies (BAV, Degenerative), and is not dependant on the location of the aneurysm (maximal dilation of the aortic root at the level of sinuses of Valsalva or maximal dilation of the ascending aorta above the sinotubular junction).
In contrast to abdominal aortic aneurysm (AAA), aneurysms of the ascending aorta are not associated with a mural thrombus, which could readily explain the presence of circulating markers of platelet and prothrombin activation.1 Also in contrast with AAA, inflammation, which predominates in the adventitia of AAA,21 is absent in the aortic wall obtained from TAAA, including the adventitia.1,22 Our peripheral measurements of plasma CRP and fibrinogen are in keeping with this observation.
It is possible that activated platelets and coagulation factors are more rapidly diluted and washed away by the particular flow conditions in the ascending aorta. Indeed, it appears that the triggering event is sufficient to initiate thrombin generation and platelet activation but insufficient to permit fibrinogen clotting and platelet aggregation. Because elevation of P-selectin, a highly procoagulant mediator,23 is only minimal, it could also limit the onset of coagulation.
The absence of any thrombus or sign of significant inflammation in TAAA raises the question of the origin of the prothrombotic markers. Our most clear-cut observation was related to the activation of platelets and prothrombin. The main trigger of the thrombin generation cascade is tissue factor (TF),24,25 which is constitutively expressed in tissues.26 Plasma TF concentrations were found to be increased in patients with large aneurysms compared to controls. This signifies that higher amounts of active TF are circulating in blood from patients with large aneurysms than in blood from controls, but that TF activity is not sufficient to generate a clot, as there was no evidence of macroscopic or microscopic thrombus in TAAA patients. The increased level of TAT is in favor of in vivo thrombin generation, which is further supported by the elevated level of sGPV, a marker of platelet activation by thrombin.27
The rate of prothrombin activation is dependent on the assembly of tenase and prothrombinase complexes, which in turn depends on the presence of surfaces enriched in negatively-charged phospholipids.28 The increased number of microparticles of platelet origin observed in association with large aneurysms is likely to provide the phosphatidylserine-enriched membranes required to favor thrombin generation.29 Microparticles are the main link between platelet activation and thrombin generation.29,30 Elevated levels of sGPV and platelet-derived microparticles in vivo indicate platelet activation by thrombin27 in TAAA. Elevated soluble CD40L (CD154), a transmembrane protein released by proteolytic cleavage in response to various stimuli,31 in the plasma of TAAA patients also suggests platelet activation. sCD40L release is directly related to platelet activation,32,33 depends on metalloproteinase activities34 and triggers TF expression on binding to CD40 on monocytes.35 Nevertheless, because CD40L can also be released by leukocytes and endothelial cells, a nonplatelet origin of this marker cannot be completely excluded in our patients. The slight but significant increase in P-selectin expression on circulating platelets provides additional evidence for a platelet activation state in TAAA. However, when compared to the situation in AAA patients,16 a lower level of proteolytic shedding probably occurs in TAAA patients, because plasma levels of soluble P-selectin were not significantly different from control levels.
In older patients (degenerative group) or BAV patients with associated valve disease, the activation detected may not be solely related to the ascending aortic aneurysm. Indeed, in the absence of cases of ascending aortic aneurysm of diameter below 45 mm in these groups, we cannot definitively rule out the presence of platelet activation even when aortic dilatation is limited. However, this activation was not observed in the control group, nor was it related to the presence of risk factors in multivariate analysis. In contrast, Marfan patients are young and without cardiovascular risk factors or valve disease. Our MFS patients were divided according to the maximal aortic diameter (45 mm) in 2 subgroups of similar age, sex, and both without risk factors or valvulopathy. The only difference between these 2 subgroups was the value of the dilation of the Valsalva sinuses, suggesting that activation of platelets and prothrombin was directly dependent on the magnitude of TAAA dilation.
The ascending aortic aneurysm location is interesting, because the normal dilation of Valsalva sinuses induces a particular, but physiological, disturbed flow. A significant dilation in this area should strongly increase these perturbations. Vortices have also been observed in vivo by magnetic resonance imaging in aneurysms of the human ascending aorta.15,36 An abrupt increase in lumen dimension leads to localized vortex phenomena characterized by a stagnation point and a recirculation zone in vitro.11,37 Jou et al reported the correlation between changes in luminal geometry and hemodynamics in fusiform intracranial aneurysms.38
The importance of rheological factors in platelet biology and hemostatic status is now well established.11,39 It was also demonstrated earlier that dilation-induced vortical flow could lead to platelet activation,14,37 via the interaction of GPIIbIIIa and fibrinogen.11,40 This phenomenon could participate in the poststenotic accumulation of platelets.41 In addition to platelets, vortices also influence red blood cell morphology and aggregate formation.11,42 In particular, red blood cells enhance platelet reactivity43 and release ADP at low shear rates,44 which could participate in platelet activation.45,46 Therefore, this relationship between arterial wall dilation, rheological disturbance, and platelet activation could account for the observed increase in plasma markers of platelet and prothrombin activation in patients with TAAA, regardless of their localization.16,47
Thrombin is able to increase endothelial cell monolayer dysfunction and permeability.48 The elevation of soluble CD146, a protein involved in endothelial cell-cell interactions49 in patients with TAA, suggests endothelial alteration.50 This is compatible with an elevation of endothelial permeability to which in vivo thrombin generation could contribute. The increase in endothelial permeability could allow convection of plasma prothombin/thrombin into the aortic wall from the blood compartment.51 Actually, we evidenced the presence of thrombin inside the pathological aortic wall using different approaches. Indeed, TAAAs are characterized histopathologically by mucoid degeneration associated with vacuole formation within the aortic media, whatever their etiology.1,52 The initial pathological process probably associates smooth muscle cell disappearance, mucoid degeneration, and extracellular matrix breakdown not linked to atherosclerosis. The release of TAT into the conditioned media indicated that active thrombin was present within the aortic media (Figure 3) and could play a role in thoracic ascending aortic aneurysm pathology.
In conclusion, large aneurysms of the ascending aorta are associated with a significant level of platelet activation and thrombin generation which can be detected via a peripheral approach. This activation process is related to the magnitude of the aortic dilation, but independent of the etiology of the aneurysm. The generation of thrombin could have a direct effect on endothelial cells and on smooth muscle cells, because we found thrombin within the ascending aortic medial layer. Exploring the role of this protease in aneurysmal progression requires further studies, and may open up the perspective of new therapeutic targets in patients with aneurysm of the ascending aorta.
|
Acknowledgments |
|---|
We thank Mary Osborne-Pellegrin for editing this article.
Sources of Funding
This study was supported by grants from the French National Research Agency (ANR), the French Society and Federation of Cardiology (SFC and FFC), the Leducq Foundation and an EU grant: No. 200647, "Fighting Aneurysmal Disease, FAD."
Disclosures
None.
|
Footnotes |
|---|
Original received October 28, 2007; final version accepted February 6, 2008.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Isselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation. 2005; 111: 816–828.
2. Boileau C, Jondeau G, Mizuguchi T, Matsumoto N. Molecular genetics of Marfan syndrome. Curr Opin Cardiol. 2005; 20: 194–200.[CrossRef][Medline] [Order article via Infotrieve]
3. Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, Allard D, Varret M, Claustres M, Morisaki H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Jondeau G, Ohta T, Kishino T, Furukawa Y, Nakamura Y, Niikawa N, Boileau C, Matsumoto N. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet. 2004; 36: 855–860.[CrossRef][Medline] [Order article via Infotrieve]
4. Pannu H, Fadulu VT, Chang J, Lafont A, Hasham SN, Sparks E, Giampietro PF, Zaleski C, Estrera AL, Safi HJ, Shete S, Willing MC, Raman CS, Milewicz DM. Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation. 2005; 112: 513–520.
5. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005; 37: 275–281.[CrossRef][Medline] [Order article via Infotrieve]
6. Zhu L, Vranckx R, Khau Van Kien P, Lalande A, Boisset N, Mathieu F, Wegman M, Glancy L, Gasc JM, Brunotte F, Bruneval P, Wolf JE, Michel JB, Jeunemaitre X. Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. Nat Genet. 2006; 38: 343–349.[CrossRef][Medline] [Order article via Infotrieve]
7. Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007; 39: 1488–1493.[CrossRef][Medline] [Order article via Infotrieve]
8. Hasham SN, Willing MC, Guo DC, Muilenburg A, He R, Tran VT, Scherer SE, Shete SS, Milewicz DM. Mapping a locus for familial thoracic aortic aneurysms and dissections (TAAD2) to 3p24-25. Circulation. 2003; 107: 3184–3190.
9. Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW. Bicuspid aortic valve is heritable. J Am Coll Cardiol. 2004; 44: 138–143.
10. Fedak PW, Verma S, David TE, Leask RL, Weisel RD, Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation. 2002; 106: 900–904.
11. Hathcock JJ. Flow effects on coagulation and thrombosis. Arterioscler Thromb Vasc Biol. 2006; 26: 1729–1737.
12. Jordan A, David T, Homer-Vanniasinkam S, Graham A, Walker P. The effects of margination and red cell augmented platelet diffusivity on platelet adhesion in complex flow. Biorheology. 2004; 41: 641–653.[Medline] [Order article via Infotrieve]
13. Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, Bauters A, Decoene C, Goudemand J, Prat A, Jude B. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003; 349: 343–349.
14. Maxwell MJ, Westein E, Nesbitt WS, Giuliano S, Dopheide SM, Jackson SP. Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation. Blood. 2007; 109: 566–576.
15. Bogren HG, Mohiaddin RH, Yang GZ, Kilner PJ, Firmin DN. Magnetic resonance velocity vector mapping of blood flow in thoracic aortic aneurysms and grafts. J Thorac Cardiovasc Surg. 1995; 110: 704–714.
16. Touat Z, Ollivier V, Dai J, Huisse MG, Bezeaud A, Sebbag U, Palombi T, Rossignol P, Meilhac O, Guillin MC, Michel JB. Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution. Am J Pathol. 2006; 168: 1022–1030.
17. Erbel R, Alfonso F, Boileau C, Dirsch O, Eber B, Haverich A, Rakowski H, Struyven J, Radegran K, Sechtem U, Taylor J, Zollikofer C, Klein WW, Mulder B, Providencia LA. Diagnosis and management of aortic dissection. Eur Heart J. 2001; 22: 1642–1681.
18. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996; 62: 417–426.[CrossRef][Medline] [Order article via Infotrieve]
19. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Zamorano JL, Angelini A, Antunes M, Fernandez MA, Gohlke-Baerwolf C, Habib G, McMurray J, Otto C, Pierard L, Pomar JL, Prendergast B, Rosenhek R, Uva MS, Tamargo J. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007; 28: 230–268.
20. Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol. 2007; 50: 1822–1834.
21. Lindholt JS, Shi GP. Chronic inflammation, immune response, and infection in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2006; 31: 453–463.[CrossRef][Medline] [Order article via Infotrieve]
22. Guo G, Booms P, Halushka M, Dietz HC, Ney A, Stricker S, Hecht J, Mundlos S, Robinson PN. Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse model and a GxxPG-containing fibrillin-1 fragment. Circulation. 2006; 114: 1855–1862.
23. Polgar J, Matuskova J, Wagner DD. The P-selectin, tissue factor, coagulation triad. J Thromb Haemost. 2005; 3: 1590–1596.[CrossRef][Medline] [Order article via Infotrieve]
24. Orfeo T, Butenas S, Brummel-Ziedins KE, Mann KG. The tissue factor requirement in blood coagulation. J Biol Chem. 2005; 280: 42887–42896.
25. Butenas S, Mann KG. Active tissue factor in blood? Nat Med. 2004; 10: 1155–1156; author reply 1156.[Medline] [Order article via Infotrieve]
26. Osterud B, Bjorklid E. Sources of tissue factor. Semin Thromb Hemost. 2006; 32: 11–23.[CrossRef][Medline] [Order article via Infotrieve]
27. Azorsa DO, Moog S, Ravanat C, Schuhler S, Follea G, Cazenave JP, Lanza F. Measurement of GPV released by activated platelets using a sensitive immunocapture ELISA-its use to follow platelet storage in transfusion. Thromb Haemost. 1999; 81: 131–138.[Medline] [Order article via Infotrieve]
28. Gerads I, Govers-Riemslag JW, Tans G, Zwaal RF, Rosing J. Prothrombin activation on membranes with anionic lipids containing phosphate, sulfate, and/or carboxyl groups. Biochemistry. 1990; 29: 7967–7974.[CrossRef][Medline] [Order article via Infotrieve]
29. Lentz BR. Exposure of platelet membrane phosphatidylserine regulates blood coagulation. Prog Lipid Res. 2003; 42: 423–438.[CrossRef][Medline] [Order article via Infotrieve]
30. Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002; 22: 1381–1389.
31. Otterdal K, Pedersen TM, Solum NO. Release of soluble CD40 ligand after platelet activation: studies on the solubilization phase. Thromb Res. 2004; 114: 167–177.[Medline] [Order article via Infotrieve]
32. Prasad KS, Andre P, Yan Y, Phillips DR. The platelet CD40L/GP IIb-IIIa axis in atherothrombotic disease. Curr Opin Hematol. 2003; 10: 356–361.[CrossRef][Medline] [Order article via Infotrieve]
33. Andre P, Nannizzi-Alaimo L, Prasad SK, Phillips DR. Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation. 2002; 106: 896–899.
34. Henn V, Steinbach S, Buchner K, Presek P, Kroczek RA. The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40. Blood. 2001; 98: 1047–1054.
35. Mach F, Schonbeck U, Bonnefoy JY, Pober JS, Libby P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation. 1997; 96: 396–399.
36. Westhoff-Bleck M, Meyer GP, Lotz J, Tutarel O, Weiss T, Rafflenbeul W, Drexler H, Schroder E. Dilatation of the entire thoracic aorta in patients with bicuspid aortic valve: a magnetic resonance angiography study. Vasa. 2005; 34: 181–185.[CrossRef][Medline] [Order article via Infotrieve]
37. Korfer S, Klaus S, Mottaghy K. Application of Taylor vortices in hemocompatibility investigations. Int J Artif Organs. 2003; 26: 331–338.[Medline] [Order article via Infotrieve]
38. Jou LD, Wong G, Dispensa B, Lawton MT, Higashida RT, Young WL, Saloner D. Correlation between lumenal geometry changes and hemodynamics in fusiform intracranial aneurysms. AJNR Am J Neuroradiol. 2005; 26: 2357–2363.
39. Nesbitt WS, Mangin P, Salem HH, Jackson SP. The impact of blood rheology on the molecular and cellular events underlying arterial thrombosis. J Mol Med. 2006; 84: 989–995.[CrossRef][Medline] [Order article via Infotrieve]
40. Goncalves I, Hughan SC, Schoenwaelder SM, Yap CL, Yuan Y, Jackson SP. Integrin alpha IIb beta 3-dependent calcium signals regulate platelet-fibrinogen interactions under flow. Involvement of phospholipase C gamma 2. J Biol Chem. 2003; 278: 34812–34822.
41. Soslau G, Schechner AJ, Alcasid PJ, Class R. Influence of vortex speed on fresh versus stored platelet aggregation in the absence and presence of extracellular ATP. Thromb Res. 2000; 97: 15–27.[CrossRef][Medline] [Order article via Infotrieve]
42. Karino T, Motomiya M. Flow through a venous valve and its implication for thrombus formation. Thromb Res. 1984; 36: 245–257.[CrossRef][Medline] [Order article via Infotrieve]
43. Santos MT, Valles J, Marcus AJ, Safier LB, Broekman MJ, Islam N, Ullman HL, Eiroa AM, Aznar J. Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment. J Clin Invest. 1991; 87: 571–580.[Medline] [Order article via Infotrieve]
44. Alkhamis TM, Beissinger RL, Chediak JR. Red blood cell effect on platelet adhesion and aggregation in low-stress shear flow. Myth or fact? ASAIO Trans. 1988; 34: 868–873.[Medline] [Order article via Infotrieve]
45. Goldsmith HL, Kaufer ES, McIntosh FA. Effect of hematocrit on adenosine diphosphate-induced aggregation of human platelets in tube flow. Biorheology. 1995; 32: 537–552.[CrossRef][Medline] [Order article via Infotrieve]
46. Valles J, Santos MT, Aznar J, Martinez M, Moscardo A, Pinon M, Broekman MJ, Marcus AJ. Platelet-erythrocyte interactions enhance alpha(IIb)beta(3) integrin receptor activation and P-selectin expression during platelet recruitment: down-regulation by aspirin ex vivo. Blood. 2002; 99: 3978–3984.
47. Frosen J, Piippo A, Paetau A, Kangasniemi M, Niemela M, Hernesniemi J, Jaaskelainen J. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke. 2004; 35: 2287–2293.
48. Birukova AA, Birukov KG, Smurova K, Adyshev D, Kaibuchi K, Alieva I, Garcia JG, Verin AD. Novel role of microtubules in thrombin-induced endothelial barrier dysfunction. Faseb J. 2004; 18: 1879–1890.
49. Bardin N, Anfosso F, Masse JM, Cramer E, Sabatier F, Le Bivic A, Sampol J, Dignat-George F. Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion. Blood. 2001; 98: 3677–3684.
50. Bardin N, Moal V, Anfosso F, Daniel L, Brunet P, Sampol J, Dignat George F. Soluble CD146, a novel endothelial marker, is increased in physiopathological settings linked to endothelial junctional alteration. Thromb Haemost. 2003; 90: 915–920.[Medline] [Order article via Infotrieve]
51. Michel JB, Thaunat O, Houard X, Meilhac O, Caligiuri G, Nicoletti A. Topological determinants and consequences of adventitial responses to arterial wall injury. Arterioscler Thromb Vasc Biol. 2007; 27: 1259–1268.
52. Schlatmann TJ, Becker AE. Histologic changes in the normal aging aorta: implications for dissecting aortic aneurysm. Am J Cardiol. 1977; 39: 13–20.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  X. Houard, Z. Touat, V. Ollivier, L. Louedec, M. Philippe, U. Sebbag, O. Meilhac, P. Rossignol, and J.-B. Michel Mediators of neutrophil recruitment in human abdominal aortic aneurysms Cardiovasc Res, June 1, 2009; 82(3): 532 - 541. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||