Role of miR-195 in aortic aneurysmal disease.

RATIONALE: Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix. OBJECTIVE: Our aim was to assess the effect of the miR-15 family on aortic aneurysm development. METHODS AND RESULTS: Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E-deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E-deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter. CONCLUSIONS: We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.

Stent graft types for endovascular repair of thoracic aortic aneurysms.

BACKGROUND: The UK prevalence of thoracic aneurysm is estimated at 10.4 per 100,000 person-years. Progressive and unpredictable enlargement can lead to rupture. Endovascular repair of thoracic aortic aneurysms involves a stent graft system being introduced via the femoral artery and manipulated within the aorta under radiological guidance. Following endograft deployment, a seal is formed at the proximal and distal landing zones to exclude the aneurysm sac from the circulation. With the increasing popularity of endovascular repair there has been an increase in the number of commercially available stent graft designs on the market. This is an update of the review first published in 2013. OBJECTIVES: This review aimed to assess the different stent graft types for endovascular repair of thoracic aortic aneurysms. SEARCH METHODS: The Cochrane Vascular Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched February 2015) and the Cochrane Register of Studies CENTRAL (2015, Issue 1). Trial databases were searched by the TSC for details of ongoing and unpublished studies. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) of stent graft types in the repair of thoracic aortic aneurysms were sought without language restriction. DATA COLLECTION AND ANALYSIS: Data collection and analysis was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: No studies were identified that met the inclusion criteria. It was not possible to assess the quality of the evidence in the absence of studies eligible for inclusion in the review. AUTHORS' CONCLUSIONS: Unfortunately, no data exist regarding direct comparisons of the performance of different stent graft types. High quality RCTs evaluating stent graft types in thoracic endovascular aneurysm repair are required.

Stent graft types for endovascular repair of abdominal aortic aneurysms.

BACKGROUND: The UK prevalence of abdominal aortic aneurysm (AAA) is estimated at 4.9% in over 65-year olds. Progressive and unpredictable enlargement can lead to rupture. Endovascular repair of AAAs involves a stent graft system being introduced via the femoral artery and manipulated within the aorta under radiological guidance. Following endograft deployment, a seal is formed at the proximal and distal landing zones to exclude the aneurysm sac from the circulation. With the increasing popularity of endovascular repair there has been an increase in the number of commercially available stent graft designs on the market. This is an update of the review first published in 2013. OBJECTIVES: This review aimed to assess the different stent graft types for endovascular repair of AAA. SEARCH METHODS: The Cochrane Vascular Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched February 2015) and the Cochrane Register of Studies (2015, Issue 1). Trial databases were searched by the TSC for details of ongoing and unpublished studies. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) of stent graft types in the repair of AAAs were sought without language restriction and in consultation with the Cochrane Vascular Group TSC. DATA COLLECTION AND ANALYSIS: We planned to conduct data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: No studies were identified that met the inclusion criteria. It was not possible to review the quality of the evidence in the absence of studies eligible for inclusion in the review. AUTHORS' CONCLUSIONS: Unfortunately, no data exist regarding direct comparisons of the performance of different stent graft types. High quality randomised controlled trials evaluating stent graft types in abdominal endovascular aneurysm repair are required.

Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis.

BACKGROUND: The magnetic resonance longitudinal relaxation time (T1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T1 signal in venous thrombi and whether changes in T1 relaxation time are informative of the susceptibility to lysis. METHODS AND RESULTS: Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T1 relaxation time correlated with thrombus composition. The mean T1 relaxation time of thrombus was shortest at 7 days following thrombus induction and returned to that of blood as the thrombus resolved. T1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS(-/-))-deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis-derived iron to paramagnetic Fe3+, which causes thrombus T1 relaxation time shortening. Studies using chemokine receptor-2-deficient mice (Ccr2(-/-)) revealed that the return of the T1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. CONCLUSIONS: The source of the T1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T1 relaxation time appears to be a good predictor of the success of thrombolysis.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Stent graft types for endovascular repair of abdominal aortic aneurysms.

BACKGROUND: The UK prevalence of abdominal aortic aneurysm (AAA) is estimated at 4.9% in over 65-year olds. Progressive and unpredictable enlargement can lead to rupture. Endovascular repair of AAAs involves a stent graft system being introduced via the femoral artery and manipulated within the aorta under radiological guidance. Following endograft deployment, a seal is formed at the proximal and distal landing zones to exclude the aneurysm sac from the circulation. With the increasing popularity of endovascular repair there has been an increase in the number of commercially available stent graft designs on the market. OBJECTIVES: This review aimed to assess the different stent graft types for endovascular repair of AAA. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 10). Trial databases were searched by the TSC for details of ongoing and unpublished studies. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) of stent graft types in the repair of AAAs were sought without language restriction and in consultation with the Peripheral Vascular Disease Group TSC. DATA COLLECTION AND ANALYSIS: We planned to conduct data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: No studies were identified that met the inclusion criteria. AUTHORS' CONCLUSIONS: Unfortunately, no data exist regarding direct comparisons of the performance of different stent graft types. Therefore, this review cannot recommend guidance to clinicians in their selection of stent graft types. High quality randomised controlled trials evaluating stent graft types in abdominal endovascular aneurysm repair are required.

Stent graft types for endovascular repair of thoracic aortic aneurysms.

BACKGROUND: The UK prevalence of thoracic aneurysm is estimated at 10.4 per 100,000 person-years. Progressive and unpredictable enlargement can lead to rupture. Endovascular repair of thoracic aortic aneurysms involves a stent graft system being introduced via the femoral artery and manipulated within the aorta under radiological guidance. Following endograft deployment, a seal is formed at the proximal and distal landing zones to exclude the aneurysm sac from the circulation. With the increasing popularity of endovascular repair there has been an increase in the number of commercially available stent graft designs on the market. OBJECTIVES: This review aimed to assess the different stent graft types for endovascular repair of thoracic aortic aneurysms. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 11). Trial databases were searched by the TSC for details of ongoing and unpublished studies. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) of stent graft types in the repair of thoracic aortic aneurysms were sought without language restriction. DATA COLLECTION AND ANALYSIS: Data collection and analysis was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: No studies were identified that met the inclusion criteria. AUTHORS' CONCLUSIONS: Unfortunately, no data exist regarding direct comparisons of the performance of different stent graft types. Therefore, this review cannot recommend guidance to clinicians in their selection of stent graft types. High quality RCTs evaluating stent graft types in thoracic endovascular aneurysm repair are required.

Hematopoietic progenitor cells and restenosis after carotid endarterectomy.

BACKGROUND AND PURPOSE: Hematopoietic progenitor cells (HPCs) may attenuate the response to vascular injury by maintaining endothelial integrity and function. Our aim was to determine whether circulating HPC number and function correlate with restenosis after carotid endarterectomy. METHODS: HPC number (CD34(+)/CD133(+) cells), early colony-forming units, migratory capacity, and senescence were analyzed in blood collected preoperatively, 1 day, and 6 weeks postoperatively. Mobilizing cytokine levels were also measured. Stenosis was assessed by duplex scanning. RESULTS: HPC numbers (P<0.001) and early colony-forming unit count (P=0.001) fell rapidly 24 hours postoperatively. Restenosis at 6 months correlated negatively with the magnitude of postoperative falls in HPC numbers (R=-0.38, P=0.013) and early colony-forming unit counts (R=-0.42, P=0.008). The migratory capacity of preoperative HPCs correlated negatively with restenosis (R=-0.48, P=0.007). Preoperative SDF1 levels correlated with falls in HPC number (R=0.42, P=0.044) and early colony-forming unit counts (R=0.56, P=0.004). CONCLUSIONS: HPC function appears to be linked to the development of carotid artery restenosis after endarterectomy. These data support the concept that HPCs have a role in regulating remodeling of the injured arterial wall.

A new imaging method for assessment of aortic dissection using four-dimensional phase contrast magnetic resonance imaging.

INTRODUCTION: Medical management of type B aortic dissection can result in progressive dilation of the false lumen and poor long-term outcome. Recent studies using models of aortic dissection have suggested flow characteristics, such as stroke volume, velocity, and helicity, are related to aortic expansion. The aim of this study was to assess whether four-dimensional phase-contrast magnetic resonance imaging (4D PC-MRI) can accurately visualize and quantify flow characteristics in patients with aortic dissection and whether these features are related to the rate of aortic expansion. METHODS: Twelve consecutive patients with medically treated type B thoracic aortic dissection underwent a three-dimensional (3D) MRI anatomy scan using a blood pool contrast agent. Two-dimensional phase contrast MRI data (2D PC-MRI) were acquired in the ascending and descending aorta and 4D PC-MRI data were acquired in the entire thoracic aorta. The 2D PC-MRI measurements were used to assess the quality of the 4D PC-MRI velocity data. Stroke volume, velocity, and the direction of flow were calculated using 4D PC-MRI and related to the rate of aortic expansion measured on contrast-enhanced computed tomography. RESULTS: Comparison of 2D PC-MRI and 4D PC-MRI measurements showed good correlation (Pearson R(2) = 0.98; 95% confidence interval [CI], 0.9818-0.9953; P < .0001) and no proportional bias (bias = 1.0 mL; standard deviation, 4.6). The median aortic growth rate was 6.1 mm/y (interquartile range [IQR], 1.1-15.1 mm/y), and this correlated well with the growth rate of the false lumen (Spearman ρ = 0.62; 95% CI, 0.06-0.89; P = .0347). False lumen thrombosis (FLT) was seen in 7 of 12 patients and was not associated with reduced aortic expansion rate (FLT present: 11.4 mm/y; IQR, 3.6-21.4) vs FLT absent: 9.9 mm/y; IQR, 3.4-24.2; Mann-Whitney P = .8763). False lumen stroke volume and velocity were associated with more rapid aortic expansion (ρ = 0.80 [95% CI, 0.39-0.94; P = .0029] and ρ = 0.59 [95% CI, 0.09-0.87; P = .0480] respectively). The position of the dominant entry tear was associated with rapid expansion, which tended to be higher with distal vs proximal entry tears (distal, 21.4 mm/y [IQR, 11.4-48.9] vs proximal, 5.5 mm/y [IQR, 3.4-16.6]; Mann-Whitney P = .096). Helical flow was seen in the false lumen in 8 of 12 patients and was related to the rate of aortic expansion (ρ = 0.83, P = .0154). CONCLUSIONS: 4D PC-MRI can be accurately applied to visualize and quantify flow characteristics in patients with aortic dissection. Stroke volume, velocity, distal dominant entry tears, and helical flow are related to the rate of aortic expansion. This study demonstrates the potential of this new imaging method. A larger prospective study is now required to measure flow characteristics and determine their predictive value for risk stratification of patients with aortic dissection.

Stent-graft limb deployment in the external iliac artery increases the risk of limb occlusion following endovascular AAA repair.

PURPOSE: To assess whether deployment of an endograft limb in the external iliac artery (EIA) increases the rate of limb occlusion following endovascular aneurysm repair (EVAR). METHODS: Interrogation of a prospectively maintained database identified 661 patients (596 men; median age 73 years, range 37-93) with infrarenal abdominal aortic aneurysm who underwent EVAR between 1996 and 2010 using Zenith stent-grafts predominately. Of these, 567 patients [56 (9.9%) women] had both endograft limbs deployed in the CIA (1203 limbs at risk), while 94 patients [9 (9.6%) women] had at least 1 limb in the EIA (22 bilateral; 116 limbs at risk). An adjunctive bare metal stent was used in 8 (9%) limbs deployed in the EIA. RESULTS: There were 31 limb occlusions, all unilateral: 17 (3%) patients in the CIA group had an occluded limb (1% of limbs at risk) vs. 14 (15%) patients in the EIA group (12% of limbs at risk; p<0.0001). The median time to occlusion was 3 months (0-60) in the CIA group and 1 month (0-36) in the EIA group. The majority of occlusions were treated by extra-anatomical revascularization, most often a femorofemoral crossover bypass. No legs were amputated following occlusion of a limb placed in the CIA, but there were 3 amputations in the EIA group (p=0.003). CONCLUSION: Deployment of endograft limbs into the EIA led to a higher rate of occlusion and leg amputation. Increased tortuosity of the EIA and a smaller caliber vessel are likely to account for the increased risk.

Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions.

Observational studies have shown that inflammatory cells accumulate within the thrombus and surrounding vein wall during the natural history of venous thrombosis. More recent studies have begun to unravel the mechanisms that regulate this interaction and have confirmed that thrombosis and inflammation are intimately linked. This review outlines our current knowledge of the complex relationship between inflammatory cell activity and venous thrombosis and highlights new areas of research in this field. A better understanding of this relationship could lead to the development of novel therapeutic targets that inhibit thrombus formation or promote its resolution.

A new method for quantification of false lumen thrombosis in aortic dissection using magnetic resonance imaging and a blood pool contrast agent.

BACKGROUND: False lumen thrombosis after aortic dissection is a major predictor of prognosis. First pass computed tomography (CT) and magnetic resonance (MR) imaging are used routinely, where the image acquisition is timed to the arrival of contrast in the proximal unaffected aorta. Delayed phase imaging is difficult to refine because flow rates in the false lumen are often very slow and highly variable between patients. Blood pool contrast agents bind to albumin and become homogenously distributed in the intravascular circulation, allowing accurate imaging of areas where flow is low. We compared first pass MR and CT with a delayed phase MR acquisition using a blood pool agent to assess whether this more accurately quantified false lumen thrombosis. METHODS: Patients with medically treated chronic type B aortic dissection and evidence of false lumen thrombosis on previous CT imaging underwent first pass CT, first pass MR, and delayed phase MR with blood pool agent. Absence of false lumen contrast enhancement was quantified to assess the apparent differences in thrombosis. Phase-contrast MR data were also obtained to assess the affect of flow velocity on false lumen contrast enhancement, and direct thrombus MR images were used to confirm the presence of thrombus. RESULTS: Twelve patients were recruited. No difference was seen in apparent thrombus volume between first pass CT and first pass MR imaging (146.9 cm(3) [SD, 88.6] vs 187.6 cm(3) [SD, 136.1], P = .1119; R(2) = .67 [95% confidence interval (CI), r = .46-.95], P = .0012). In all patients, the volume of thrombus derived from first pass acquisitions was greater than the volume derived from delayed phase MR imaging with blood pool agent: first pass CT (paired t test, P = .0007; mean difference = 83.4 cm(3) [95% CI, 44.1-122.6]) and first pass MR (paired t test, P = .0009; mean difference = 124.0 cm(3) [95% CI, 63.2-184.9]). The difference in thrombus volume between first pass and delayed phase MR imaging with blood pool agent correlated significantly with the mean velocity of flow in the false lumen, with lower flow related to a greater difference (R(2) = .61, P = .0028 [95% CI, r = -.94--.37]). Direct thrombus MR images were able to correctly discriminate between thrombus and blood and matched the area of contrast absence on delayed phase MR with blood pool agent images. CONCLUSION: First pass techniques to assess false lumen thrombosis in aortic dissection consistently overestimate the apparent thrombus volume by five to six times. This has implications for interpretation of cohort studies and clinical trials that use false lumen thrombosis as an outcome measure. We recommend delayed phase MR imaging with a blood pool agent when accurate assessment of false lumen thrombosis is required.

Endovascular treatment of acute aortic syndrome.

BACKGROUND: The term acute aortic syndrome (AAS) encompasses a range of conditions that have a risk of imminent aortic rupture and where delays in treatment result in increased mortality. Endovascular treatment offers an attractive alternative to open surgery but little is known about the durability of the repair and the factors that predict mortality. METHODS: Prospective data were collected for a cohort of 110 consecutive patients with endovascular treatment for AAS. Patient and procedural characteristics were related to short- and midterm outcome using multivariate logistic regression analysis. RESULTS: There were 75 men and 35 women with a median age of 68 (range 57-76) years. The pathologies treated were acute dissection (35), symptomatic aneurysm (32), infected aneurysm (18), transection (12), chronic dissection (9), penetrating ulcer (3), and intramural hematoma (1). Thirty-day mortality was 12.7% and this was associated with hypotension (odds ratio [OR], 5.25), use of general anesthetic (OR, 5.23), long procedure duration (OR, 2.03), and increasing age (OR, 1.07). The causes of death were aortic rupture (4), myocardial infarction (4), stroke (3), and multisystem organ failure (3). The stroke and paraplegia rates were 7.3% and 6.4%, respectively. The 1-year survival was 81% and the 5-year survival 63%. Secondary procedures were required in 13 (11.8%) patients. Factors associated with death at 1 year were presence of an aortic fistula (OR, 9.78), perioperative stroke (OR, 5.87), and use of general anesthetic (OR, 3.76); and at 5 years were aortic fistula (OR, 12.31) and increasing age (OR, 1.06). CONCLUSIONS: Acute aortic syndrome carries significant early and late mortality. Emergency endovascular repair offers a minimally invasive treatment option associated with acceptable short and midterm results. Continued surveillance is important as secondary procedures and aortic-related deaths continue to occur throughout the follow-up period.

Accelerated aortic imaging using small field of view imaging and electrocardiogram-triggered quadruple inversion recovery magnetization preparation.

PURPOSE: To accelerate and optimize black blood properties of the quadruple inversion recovery (QIR) technique for imaging the abdominal aortic wall. MATERIALS AND METHODS: QIR inversion delays were optimized for different heart rates in simulations and phantom studies by minimizing the steady state magnetization of blood for T(1) = 100-1400 ms. To accelerate and improve black blood properties of aortic vessel wall imaging, the QIR prepulse was combined with zoom imaging and (a) "traditional" and (b) "trailing" electrocardiogram (ECG) triggering. Ten volunteers were imaged pre- and post-contrast administration using a conventional ECG-triggered double inversion recovery (DIR) and the two QIR implementations in combination with a zoom-TSE readout. RESULTS: The QIR implemented with "trailing" ECG-triggering resulted in consistently good blood suppression as the second inversion delay was timed during maximum systolic flow in the aorta. The blood signal-to-noise ratio and vessel wall to blood contrast-to-noise ratio, vessel wall sharpness, and image quality scores showed a statistically significant improvement compared with the traditional QIR implementation with and without ECG-triggering. CONCLUSION: We demonstrate that aortic vessel wall imaging can be accelerated with zoom imaging and that "trailing" ECG-triggering improves black blood properties of the aorta which is subject to motion and variable blood flow during the cardiac cycle.

Hypoxia and upregulation of hypoxia-inducible factor 1{alpha} stimulate venous thrombus recanalization.

OBJECTIVE: Angiogenic factors are expressed within thrombus during resolution, but the primary stimulus for neovascularization is unknown. Our aims were to determine whether (1) hypoxia and hypoxia-inducible factor 1α (HIF1α) are induced in resolving thrombus, (2) this stimulates angiogenic factor production, and (3) upregulating HIF1α enhances thrombus resolution and vein recanalization. METHODS AND RESULTS: Oxygen tension in the thrombus was negatively correlated with HIF1α levels (Spearman correlation [RS] = -0.77, P<0.0001), whereas HIF1α levels positively correlated with vascular endothelial growth factor (VEGF) expression (Pearson correlation [R] = 0.85, P<0.0005), during resolution in a murine model. HIF1α (P<0.005), VEGF (P<0.005), and VEGF receptor 1 (VEGFR1) (P<0.05) expression was 2-fold greater in the thrombus of mice treated with the prolyl hydroxylase domain inhibitor L-mimosine compared with controls. The levels of 13 other HIF1-mediated angiogenic factors were also increased. Thrombus weight (P<0.001) and volume (P<0.05) were reduced by a third in l-mimosine-treated mice compared with controls, whereas vein recanalization (P<0.005) and thrombus neovascularization (P<0.001) were 2-fold greater, and this was associated with increased inflammatory cell content. CONCLUSIONS: Hypoxia and HIF1α are induced in the naturally resolving thrombus and correlate with increased angiogenic factor expression. Upregulation of HIF1α enhances thrombus resolution and vein recanalization. HIF1α may represent a novel target for treatments that promote resolution and recanalization and reduce the incidence of post-thrombotic syndrome.

The monocyte/macrophage as a therapeutic target in atherosclerosis.

It is now clear that the monocyte/macrophage has a crucial role in the development of atherosclerosis. This cell appears to be involved in all stages of atherosclerotic plaque development and is increasingly seen as a candidate for therapeutic intervention and as a potential biomarker of disease progression and response to therapy. The main mechanisms related to the activity of the monocyte/macrophage that have been targeted for therapy are those that facilitate recruitment, cholesterol metabolism, inflammatory activity and oxidative stress. There is also increasing evidence that there is heterogeneity within the monocyte/macrophage population, which may have important implications for plaque development and regression. A better insight into how specific phenotypes may influence plaque progression should facilitate the development of novel methods of imaging and more refined treatments.

3D T(1)-mapping for the characterization of deep vein thrombosis.

PURPOSE: The aim of this work was to investigate fast T (1)-mapping for the characterization of deep vein thrombosis (DVT). METHODS: The accuracy and reproducibility of the T (1)-mapping sequence was tested in phantoms and in 8 healthy volunteers on a 1.5 T clinical scanner using a 32-channel array coil. Furthermore, the feasibility of the technique was tested in 5 patients diagnosed with DVT by measuring the volume and T (1) values of the thrombus at 5 time points over a period of 6 months. RESULTS: The results of the phantom and volunteer study showed a high accuracy and reproducibility for the quantification of T (1). The resolution of the T (1)-maps was high enough to identify small anatomical structures. T (1) values derived for normal blood and various other tissues were comparable to those reported in the literature. In all patients, the T (1) times of thrombi showed decreased values (T (1) = 843 +/- 91 ms) in the acute phase and recovered back to normal values of blood (T (1) = 1,317 +/- 36 ms) after 6 months. CONCLUSIONS: Measurement of all relevant T (1) values of acute thrombi and normal blood achieved accurate and reproducible results in vivo. Fast T (1) quantification of the thrombus can provide information about tissue characteristics such as thrombus resolution. Such a quantitative MRI technique may be valuable in studying the factors that influence natural resolution and in evaluating treatment effects that enhance this process.

Endovascular grafting of the thoracic aorta, an evolving therapy: ten-year experience in a single centre.

BACKGROUND: Surgical therapy for the thoracic aorta carries a high morbidity and mortality. Endovascular therapy for aneurysms and its adaptation to the thoracic aorta over the past 10 years is an exciting advance. This is a retrospective review of endovascular grafting of the thoracic aorta during the past decade at Royal Prince Alfred Hospital and the outcomes achieved over this period. METHODS: A retrospective review of all patients at our institution who underwent endovascular grafting of the thoracic aorta between March 1995 and March 2005 was carried out. Data were analysed using Stata version 8.0 (Stata corporation, College Station, TX, USA). RESULTS: Sixty-five patients underwent endovascular stent grafting of the thoracic aorta. The indications were degenerative aneurysm (31), Stanford type B dissection (23) both acute (12) and chronic (11), traumatic transection (9) and penetrating ulcer (2). There were no conversions to open repair. Twenty-two patients required additional procedures, six of which were unplanned. The median age was 65 (range 18-85), 68% of patients were men. The median procedure time was 115 min (range 55-240 min). Mean hospital stay was 9.8+/-7.3 days and high dependency/intensive care unit stay 1.5+/-3.2 days. Thirty-day mortality was 0 in 41 for elective cases (one patient (2.5%) died 37 days post-procedure) and 12% (3 of 25) for emergency cases. Complications occurred in 20 of 41 (49%) elective cases and 14 of 24 (58%) emergency cases within the first 30 days. The most frequent major complications were neurological including paraplegia (transient 2 of 65, permanent (2 of 65)) and stroke (4 of 65). Other complications included endoleak (12 of 65), acute renal failure (1 of 65), and brachial artery false aneurysm (1 of 65). The mean length of follow up was 22.5 months (range, 1-97 months). Six patients required further endovascular procedures for persistent endoleak or ongoing perfusion of chronic dissection. Late deaths (>30 days) related to the endovascular treatment occurred in two patients (3%). CONCLUSION: Endovascular grafting of the thoracic aorta is an evolution in the treatment of thoracic aortic pathology. The results of elective endovascular grafts were acceptable. Emergency procedures had a higher incidence of complications and death. Improvement in graft technology, design and deployment are required.

The role of neovascularisation in the resolution of venous thrombus.

Deep vein thrombosis (DVT) can give rise to chronic debilitating complications, which are expensive to treat. Anticoagulation, the standard therapy for DVT, prevents propagation, but does not remove the existing thrombus, which undergoes slow natural resolution. Alternative forms of treatment that accelerate resolution may arise from a better understanding of the cellular and molecular pathways that regulate the natural resolution of thrombi. This review will outline our current understanding of the mechanisms of thrombus resolution and the role of neovascularisation in this process. Novel experimental treatments that may one day find clinical use are also discussed. The process of thrombus resolution resembles wound healing. The mainly monocytic inflammatory infiltrate, which develops, is associated with the appearance of vascular channels. These cells may drive resolution by encouraging angiogenesis, which contributes to restoration of the vein lumen. Significant numbers of bone marrow-derived progenitor cells have also been found in naturally resolving thrombi, but their precise phenotype and their role in thrombus recanalisation is unclear. Enhanced thrombus neovascularisation and rapid vein recanalisation have been achieved in experimental models with proangiogenic agents. Recent reports of the role of bone marrow-derived progenitor cells in the revascularisation of ischaemic tissues suggest that it may be possible to obtain the same effect by delivering pluripotent or lineage specific stem cells into thrombus. These cells could contribute to thrombus recanalisation by expressing a variety of proangiogenic cytokines or by lining the new vessels that appear within the thrombus.

Expanding Horizons for Abdominal Aortic Aneurysms.

Recent technological advances have allowed researchers to interrogate the genetic basis of abdominal aortic aneurysms in great detail. The results from these studies are expected to transform our understanding of this complex disease with both multiple genetic and environmental risk factors. Clinicians need to keep abreast of these genetic findings and understand the implications for their practice. Patients will become increasingly informed on genetic risk, and a new era of individualized risk assessment for AAA is just beginning. This brief update aims to provide the clinician with a succinct précis of the recent progress in this area.