Subsequent Aneurysm Formation Research Articles

Greater TIMP-1 protein levels and neointimal formation represent sex-dependent cellular events limiting aortic vessel expansion in female rats.

Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and neointimal growth secondary to a reduction of medial elastin content represent sex-dependent events limiting aortic vessel expansion in females. TIMP-1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP-2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2-treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re-entered the G2-M phase whereas VSMC cell cycle re-entry was attenuated in the CaCl2-treated infrarenal aorta of male rats. Thus, greater TIMP-1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2-treatment of the infrarenal aorta of female rats represents a sex-dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.

Vertebral Artery Dissection Mimicking Migraine: A Case Report

Vertebral artery dissection (VAD) is caused by an intimal tear that leads to bleeding into the vascular wall, which may cause vascular occlusion by thrombus formation and subsequent distal emboli (leading to ischemic stroke), aneurysm formation and subarachnoid hemorrhage. Cervical artery dissections (either carotid or vertebral artery dissection) are an important cause of stroke in patients under 50-years of age. Headache with or without neck pain is a common symptom. Usually, it occurs with focal neurological signs but sometimes it may occur without any neurological deficits and may mimic migraine. Often it occurs spontaneously without trauma but sometimes there is history of minor traumas, sudden neck movements or chiropractic manipulation. Imaging modalities include magnetic resonance imaging (MRI) brain, magnetic resonance angiography (MRA), and computed tomography angiography (CTA). Treatment involves anticoagulation or antiplatelet agents.

Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3\u2013CCR5 axis

Inflammatory mediators such as cytokines and chemokines are crucially involved in the development of abdominal aortic aneurysm (AAA). Here we report that CaCl2 application into abdominal aorta induces AAA with intra-aortic infiltration of macrophages as well as enhanced expression of chemokine (C-C motif) ligand 3 (CCL3) and MMP-9. Moreover, infiltrating macrophages express C-C chemokine receptor 5 (CCR5, a specific receptor for CCL3) and MMP-9. Both Ccl3−/− mice and Ccr5−/− but not Ccr1−/− mice exhibit exaggerated CaCl2-inducced AAA with augmented macrophage infiltration and MMP-9 expression. Similar observations are also obtained on an angiotensin II-induced AAA model. Immunoneutralization of CCL3 mimics the phenotypes observed in CaCl2-treated Ccl3−/− mice. On the contrary, CCL3 treatment attenuates CaCl2-induced AAA in both wild-type and Ccl3−/− mice. Consistently, we find that the CCL3–CCR5 axis suppresses PMA-induced enhancement of MMP-9 expression in macrophages. Thus, CCL3 can be effective to prevent the development of CaCl2-induced AAA by suppressing MMP-9 expression.

Connective Tissue Abnormalities in Patients with Ruptured Intracranial Aneurysms and No Known Systemic Connective Tissue Disorder

Defect in internal elastic lamina, defect in tunica media, and the amount of collagen and elastin play a role in vessel wall weakening leading to aneurysm formation. A similar picture may be found in connective tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome (EDS), neurofibromatosis type 1, and Loeys-Dietz syndrome (LDS), where there is a predominant disorder of collagen formation/maturation. Histopathology of skin and the superficial temporal artery (STA) was done. All specimens were obtained during craniotomy for ruptured aneurysm clipping or other indicated procedures (for control subjects). Parameters in skin biopsy seen were epithelial thickness, dermal collagen thickness, and so forth. For the STA, parameters such as intimal thickness, intimal proliferation, thickness of media, and so forth were studied. Twenty cases and twenty control subjects were studied. The mean age of the study population was 40.5 years. Salient findings on skin biopsy in patients of intracranial aneurysms (IAs) (cases) were haphazard orientation of collagen, inflammation in the subepidermal layer, increased dermal collagen thickness, and reduced and/or fragmented elastic fibers. Prominent findings on vessel wall biopsy were intimal proliferation, reduplication of internal elastic lamina, reduced and/or fragmented elastin, and vacuolation of smooth muscle cells. The average number of aberrations per patient was significantly higher in cases than control subjects. The histologic changes seen in skin and the STA in cases of IAs signify a weak connective tissue. Some of these findings are also seen in known connective tissue disorders such as Marfan syndrome, EDS, neurofibromatosis type 1, and LDS. The connective tissue abnormalities found in patients with IAs may be congenital, which gets further accentuated by known risk factors leading to weak vessel wall and subsequent aneurysm formation.

Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? CON.

Fistulas continue to be promoted as the vascular access of choice due to their lower complication rates as compared with catheters (1,2). However, depending on the fistula cannulation method, the infection risk can compared with that of a catheter. Traditionally, cannulation is an area most physicians tend to ignore; instead, the choice and technique of cannulation is routinely left to nurses. However, given the pain, fear, and anxiety with cannulation that most hemodialysis patients experience (3–⇓5), all health care providers should pay more attention to needling. Furthermore, cannulation and its associated mishaps can lead to fistula complications of infection, and decreased patency. The most common method of cannulation among maintenance hemodialysis patients is the rope ladder technique, which rotates needling sites along the full length of the fistula. The area wall technique, where favored regions are repeatedly needled, is actively discouraged due to progressive weakness in the vessel wall and subsequent aneurysm formation (6). Buttonhole cannulation is more often used in home hemodialysis and it was first introduced as a measure to cannulate a fistula with a limited area for needling (7). Buttonhole involves a constant site of needling that, over time, leads to an epithelized track into which a blunt needle is inserted. Since its first introduction almost 50 years ago by Dr Twardoski and his head nurse (Sister Kumara), buttonhole has continued to garner widespread enthusiasm. Support for its use has been mostly promoted by observational data and poor-quality methodology studies showing beneficial effects on pain and fewer needling complications. Nephrology societies (8,9) (renal.org/guidelines) still recommend buttonhole use as a means to reduce pain and increase longevity. In order to promote a novel cannulation technique over the standard of care, there should be evidence of benefit and a lack of demonstrable …

Adeno-associated Virus Vector-mediated Interleukin-10 Induction Prevents Vascular Inflammation in a Murine Model of Kawasaki Disease

Kawasaki disease (KD), which is the leading cause of pediatric heart disease, is characterized by coronary vasculitis and subsequent aneurysm formation. Although intravenous immunoglobulin therapy is effective for reducing aneurysm formation, a certain number of patients are resistant to this therapy. Because interleukin-10 (IL-10) was identified as a negative regulator of cardiac inflammation in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS), we investigated the effect of IL-10 supplementation in CAWS-induced vasculitis. Mice were injected intramuscularly with adeno-associated virus (AAV) vector encoding IL-10, then treated with CAWS. The induction of AAV-mediated IL-10 (AAV-IL-10) significantly attenuated the vascular inflammation and fibrosis in the aortic root and coronary artery, resulting in the improvement of cardiac dysfunction and lethality. The predominant infiltrating inflammatory cells in the vascular walls were Dectin-2+CD11b+ macrophages. In vitro experiments revealed that granulocyte/macrophage colony-stimulating factor (GM-CSF) induced Dectin-2 expression in bone marrow-derived macrophages and enhanced the CAWS-induced production of tumor necrosis factor-α (TNF-α) and IL-6. IL-10 had no effect on the Dectin-2 expression but significantly inhibited the production of cytokines. IL-10 also inhibited CAWS-induced phosphorylation of ERK1/2, but not Syk. Furthermore, the induction of AAV-IL-10 prevented the expression of TNF-α and IL-6, but not GM-CSF and Dectin-2 at the early phase of CAWS-induced vasculitis. These findings demonstrate that AAV-IL-10 may have therapeutic application in the prevention of coronary vasculitis and aneurysm formation, and provide new insights into the mechanism underlying the pathogenesis of KD.

MRI Vessel Wall Imaging and Treatment of an Aneurysm at the Atlanto-Axial Segment of an Aberrant Vertebral Artery

We report a case of unique location of an aneurysm at the atlanto-axial extradural segment of a unilateral aberrant vertebral artery. The MRI vessel wall imaging findings and possible mechanism of aneurysm formation were discussed. A 5 mm extracranial vertebral artery aneurysm located at the interlaminar space between C1 and C2 was diagnosed in a woman presenting with occipital headache. The index vertebral artery ran an aberrant course at the V3 segment, where it entered the dura between C1 and C2 instead of the usual atlanto-occipital space. MR vessel wall imaging showed homogenous wall enhancement of the aneurysm sac. We surmise the anomalous course of the vertebral artery subjected the V3 segment to repeated shearing force secondary to the atlanto-axial rotational neck movement. This led to vessel wall trauma and inflammation, and subsequent aneurysm formation. The aneurysm was successfully treated with endovascular coiling with resolution of symptoms.

Native Aortic Valve Endocarditis Complicated by Pseudoaneurysm of Mitral-Aortic Intervalvular Fibrosa

Pseudoaneurysm of mitral-aortic intervalvular fibrosa (PA-MAIVF) is a rare complication of native aortic valve endocarditis. This region is a relatively avascular area and prone to infection during endocarditis and subsequent aneurysm formation. The rupture into the pericardial cavity and left atrium or aorta, systemic embolism, myocardial infarction secondary to left coronary compression, and sudden death are the reported complications. Herein, we present a 9-year-old boy who was diagnosed with bicuspid aortic valve endocarditis complicated by PA-MAIVF, cerebral embolism, and hemorrhage. PA-MAIVF was visualized by both two- and three-dimensional transthoracic echocardiography and ruptured into pericardial space causing a fatal outcome.

Overview of large animal myocardial infarction models (review)

There are several experimental models for the in vivo investigation of myocardial infarction (MI) in small (mouse, rat) and large animals (dog, pig, sheep and baboons). The application of large animal models raises ethical concerns, the design of experiments needs longer follow-up times, requiring proper breeding and housing conditions, therefore resulting in higher cost, than in vitro or small animal studies. On the other hand, the relevance of large animal models is very important, since they mostly resemble to human physiological and pathophysiological processes. The first main difference among MI models is the method of induction (open or closed chest, e.g. surgical or catheter based); the second main difference is the presence or absence of reperfusion. The former (i.e. reperfused MI) allows the investigation of reperfusion injury and new catheter based techniques during percutaneous coronary interventions, while the latter (i.e. nonreperfused MI) serves as a traditional coronary occlusion model, to test the effects of new pharmacological agents and biological therapies, as cell therapy. The reperfused and nonreperfused myocardial infarction has different outcomes, regarding left ventricular function, remodelling, subsequent heart failure, aneurysm formation and mortality. Our aim was to review the literature and report our findings regarding experimental MI models, regarding the differences among species, methods, reproducibility and interpretation.

Peri-stent aneurysm formation following a stent implant for stenotic intracranial vertebral artery dissection: a technical report of two cases successfully treated with coil embolization

Although stenting for stenotic vertebral artery dissection (VAD) improves compromised blood flow, subsequent peri-stent aneurysm (PSA) formation is not well-known. We report two cases with PSA successfully treated with coil embolization. Three patients with stenotic intracranial VAD underwent endovascular angioplasty at our institution because they had acute infarction in posterior circulation territory and clinical evidence of hemodynamic insufficiency. In two of three patients balloon angioplasty at first session failed to relieve the stenosis, and a coronary stent was implanted. Angiography immediately after stenting showed no abnormality in case 1 and minimal slit-like projection at proximal portion of the stent in case 2. Angiography obtained 16 months after the stenting revealed PSA in case 1. In case 2, angiography performed 3 months later showed that the projection at proximal portion enlarged and formed an aneurysm outside the stent. Because follow-up angiographies showed growth of the aneurysm in both cases, endovascular aneurysmal embolization was performed. We advanced a microcatheter into the aneurysm through the strut of existing stent and delivered detachable coils into the aneurysm lumen successfully in both cases. The post-procedural course was uneventful, and complete obliteration of aneurysm was confirmed on angiography in both cases. Stenting for stenotic intracranial VAD may result in delayed PSA; therefore, follow-up angiographies would be necessary after stenting for stenotic intracranial arterial dissection. Coil embolization through the stent strut would be a solution for enlarging PSA.

Abstract 100: Periaortic Leptin Induces Local Medial Degeneration in ApoE -/- Mice Preceding Aneurysm Formation

Background: Leptin (Ob) is a proatherogenic hormone involved in vessel wall remodeling. We hypothesized that Ob locally synthesized in the abdominal aorta regulates vascular remodeling mediators (TGFβ, MMPs) thereby sensitizing the aorta to subsequent aneurysm formation. Methods: Human abdominal aortic aneurysm (AAA) wall (n=10), and non-dilated aortic (n=3) samples underwent real time qPCR mRNA analysis for Ob and Ob receptor (ObR), and immunohistochemical analysis (SM-αactin, CD68, Ob, and ObR). Plasma samples obtained prior to AAA surgery were analyzed for Ob and ObR antigen (n=20). A novel mouse model was utilized to elucidate the role of Ob in AAA formation. Local Ob synthesis was simulated by point application of 20μg Ob slow release (n=10), or placebo (n=10) compound at the peri-vascular space of the para-visceral aorta in ApoE -/- mice on a Western diet. Serial ultrasound examinations on days 0, 14, 28, 35, and 42 assessed aortic diameter at reference locations. A parallel group (n=10), randomized to Ob or placebo treatment was euthanized on day 5 for aortic mRNA analysis. Results: Increased Ob mRNA levels and immunoreactivity were evident in human AAA wall samples vs controls. Plasma Ob and ObR levels were within normal range. Ob treated mice demonstrated augmented growth rate of luminal aortic diameter in the para-visceral segment on day 28 (p=0.0001). Aortas analyzed 5 days after Ob deployment revealed suppressed TGFβ mRNA (p=0.002), while MMP-9 transcript was up-regulated (p=0.047). Ob treated mice euthanized on day 45 demonstrated localized aortic derangement of elastic fibers and loss of SM-αActin (p=0.07), alongside with increased MMP-9 (p=0.02), MMP-12 (p=0.001) antigen, and augmented adventitial macrophage infiltration. Conclusions: Ob is locally synthesized in human AAA wall. Peri-aortic Ob modulates the vessel wall in ApoE -/- mice, inducing medial degeneration at the para-visceral region. Mechanistically, the observed derangement of ECM components was associated with suppressed TGFβ mRNA, and up-regulated MMP-9 synthesis. These data suggest novel mechanistic links between Ob and human AAA formation.

Extracranial infected carotid artery aneurysm

Infected aneurysms of the extracranial carotid arteries are rare. This is a case report of a 63-year-old female who developed an infected internal carotid artery aneurysm due to group B Streptococcus ten days after a dental procedure. She was successfully treated with excision of the aneurysm and common to internal carotid artery bypass with greater saphenous vein.

Thoracic aortic dissection: are matrix metalloproteinases involved?

Thoracic aortic dissection, one of the major diseases affecting the aorta, carries a very high mortality rate. Improving our understanding of the pathobiology of this disease may help us develop medical treatments to prevent dissection and subsequent aneurysm formation and rupture. Dissection is associated with degeneration of the aortic media. Recent studies have shown increased expression and activation of a family of proteolytic enzymes-called matrix metalloproteinases (MMPs)-in dissected aortic tissue, suggesting that MMPs may play a major role in this disease. Inhibition of MMPs may be beneficial in reducing MMP-mediated aortic damage associated with dissection. This article reviews the recent literature and summarizes our current understanding of the role of MMPs in the pathobiology of thoracic aortic dissection. The potential importance of MMP inhibition as a future treatment of aortic dissection is also discussed.

Mycotic aneurysm of the posterior tibial artery – a rare complication of bacterial endocarditis: a case report

IntroductionDistal arterial embolisation and subsequent aneurysm formation are rare occurrences and most are secondary to trauma. We have found no case reports that describe posterior tibial aneurysm formation secondary to bacterial endocarditis.Case presentationWe report the case of a 47-year-old Caucasian man who, 2 years after an episode of subacute bacterial endocarditis, presented with signs and symptoms consistent with posterior tibial aneurysm formation.ConclusionPosterior tibial aneurysm formation is a rare occurrence, most commonly occurring after trauma and, although other causes have been described, to our knowledge, endocarditis has not been implicated before, and as such should therefore be borne in mind when dealing with cases where no obvious aetiology is evident.

Transiently heightened angiotensin II has distinct effects on atherosclerosis and aneurysm formation in hyperlipidemic mice

Experimentally sustained increase in angiotensin II (AngII) promotes tissue destruction in various cardiovascular disorders. We examined whether transiently heightened AngII affects subsequent atherosclerosis and aneurysm formation. AngII or saline was administered for 2 weeks to apolipoprotein E (apoE)-deficient mice. Mice were sacrificed at the end of the 2-week infusion or 6- or 14 weeks later. Short-term AngII did not affect atherosclerosis immediately following the infusion or 6 weeks later. By contrast, 14 weeks after infusion there was remarkably more atherosclerosis in previously AngII-exposed mice. Preceding the build up of atherosclerotic lesions, AngII-exposure increased mRNA expression and immunostaining of monocyte chemoattractant protein-1 (MCP-1) and its receptor, CCR2. This was followed by greater macrophage-positivity in AngII-exposed aortae. In contrast to the delayed effects on atherosclerosis, 20% of mice were found to have abdominal aneurysms at the end of AngII-exposure. This effect was not contingent on blood pressure. Moreover, despite amplification in atherosclerosis following AngII, no aneurysms were found 14 weeks later. Our studies reveal that even transient exposure to AngII primes the vessel for subsequent amplification of atherosclerosis which involves activation of MCP-1/CCR2 and influx of macrophages into the nascent atherosclerotic plaque. By contrast, transient AngII-exposure causes prompt aneurysm formation that does not parallel atherosclerosis and disappears even in the face of progressively greater atherosclerotic lesions.

Cryopreservation Prevents Arterial Allograft Dilation

Historically, immune-mediated degradation and subsequent aneurysm formation have limited the usefulness of cryopreserved arterial allografts. This study tested the hypothesis that modern cryopreserved arterial allografts are protected from immune-mediated dilation. Abdominal aortas were harvested from anesthetized rats (Lewis and Brown-Norway) for immediate implantation or cryopreservation. Subsequently, Lewis rats underwent infrarenal aortic replacement with either an acutely harvested or a cryopreserved graft. There were four experimental groups: (1) acutely harvested isografts (Iso; n = 6), (2) cryopreserved isografts (C-Iso; n = 6), (3) cryopreserved allografts (C-Allo; n = 6), and (4) acutely harvested allografts (Allo; n = 6). All grafts were explanted at 8 weeks. A video camera and edge detection software were used to measure systolic and diastolic in vivo graft diameter (d). Measurement of arterial blood pressure (p) allowed calculation of compliance (Dd/Dp). Tail-cuff plethysmography was used to assess graft patency at 1 week. Graft diameter and blood pressure measurements were repeated at harvest. All harvested grafts were examined histologically. Our results showed that cryopreservation prevented immune-mediated dilation in arterial allografts in our 8-week rat implant model. Furthermore, the compliance of the cryopreserved grafts and was similar to that of controls. Further investigation is needed to delineate the exact mechanism of these potential clinically significant findings.

Aortic aneurysm resulting from umbilical artery catheterization: Case report, literature review, and management algorithm

Aortic aneurysms in infants and children are quite rare. The use of umbilical artery catheters in the management of critically ill neonates has been associated with infection and subsequent aneurysm formation. There have been 46 cases reported (including our own); most of the aneurysms have been located in the abdominal aorta and have displayed saccular morphology. Through an analysis of the literature, we identified two factors that had significant correlation with improved survival: diagnosis before surgery and surgical repair (P <.05). This report presents the case of a 23-day-old neonate with an abdominal aortic aneurysm and hypertension. On the basis of our literature review, we offer a management algorithm for this rare but very serious complication of umbilical artery catheterization. (J Vasc Surg 2001;33:419-24.)

Aneurysmal and occlusive atherosclerosis of the human abdominal aorta

Purpose: The purpose of this study was to assess atherosclerotic plaque deposition and aortic wall responses in the abdominal aorta in relation to the development of aneurysmal and occlusive disease in the infrarenal aorta. Methods: Morphologic differences at five standardized locations in the infrarenal aorta in 67 pressure perfusion–fixed male cadaver aortas (aged, 41-98 years; mean, 66 years) were studied and compared with the supraceliac segment. Quantitative computer-assisted morphometry of histologic sections included measurement of plaque area, lumen area, lumen diameter, media thickness, number of medial elastic lamellae, and the area encompassed by the internal elastic lamina that best represents the artery size of each segment. The ratio of the supraceliac segment to the midabdominal segment (normally greater than 1.3) was used to define three groups: Group I (normal): ratio greater than or equal to 1.30 (n = 31); Group II (intermediate): ratio greater than or equal to 1.20 but less than 1.30 (n = 20); and Group III: ratio less than 1.20 (n = 16), which represented dilated midabdominal aortas. There was no significant difference in age among the groups. Results: Group I had minimal intimal plaque and little gross evidence of atherosclerosis. Group II had increased intimal plaque compared with Group I (P <.01) and gross evidence of atherosclerosis, which was maximally localized in the distal aorta; there was no aortic enlargement or thinning of the media underneath the plaque. Group III had more intimal plaque than Group I (P <.01) and Group II (P <.01) and was associated with localized aortic enlargement and media thinning compared with Group I (P <.05) and Group II (P <.01). Increasing intimal plaque in Group III correlated with an increase in lumen diameter (r = 0.61, P <.05), but this relationship was not significant in Group I and Group II. The aortic media in Group III had a reduced number of medial elastic lamellae, was reduced in thickness, and was more exposed to increased wall stress than the aortas in Groups I and II. Conclusion: These results suggest that there may be different local responses to atherosclerosis in the abdominal aorta in human beings. Plaque deposition associated with localized dilation, thinning of the media, and loss of medial elastic lamellae may predispose that segment of aorta to subsequent aneurysm formation. Plaque deposits without media thinning, without loss of elastic lamellae, and without artery wall dilation may predispose the aorta, in the event of continuing plaque accumulation, to the development of lumen stenosis. (J Vasc Surg 2001;33:91-6.)

Isolated iliac artery aneurysms in patients with or without previous abdominal aortic aneurysm repair

Background: Isolated iliac artery aneurysms (IAA) in patients with or without previous abdominal aortic aneurysm (AAA) repair are rare. We wanted to compare the presentation, distribution, treatment, outcome and patterns of subsequent aneurysm formation in these patients. Methods: We retrospectively reviewed patients with isolated IAA over a 10-year period. Patients with primary isolated IAA (group 1) were compared with patients who presented with IAA after previous AAA repair (group 2). Results: There were 23 patients in each group. Demographics and comorbidities were similar. No aneurysms were detected outside of the iliac system in group 1; 22% of patients in group 2 had other aneurysms. The mean time after AAA repair to IAA diagnosis was 8.8 ± 3.2 years for operated on patients. The in-hospital mortality was 0% for elective cases and 50% for emergency cases for both groups. Three patients in group 2 (13%) developed new aneurysms during follow-up, whereas the only new aneurysm in group 1 was a contralateral IAA. Conclusions: Patients with new IAA after AAA repair have a greater tendency to develop further aneurysms in other sites, synchronously or metachronously. The time to detection of new IAA after AAA repair is at least 5 years in most cases. In both groups, a quarter to a third of patients present with rupture, with a resultant mortality of 30% to 50%, whereas those operated on electively have minimal morbidity and almost no mortality.

Ruptured mediastinal bronchial artery aneurysm: A dilemma of diagnosis and therapeutic approach

Ruptured mediastinal bronchial artery aneurysm: A dilemma of diagnosis and therapeutic approach