Abstract MP154: Deletion of the Duffy Antigen Receptor for Chemokines (DARC) Confers Protection Against Abdominal Aortic Aneurysm (AAA) Formation

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Tyler W Benson ◽  
Tetsuo Horimatsu ◽  
Mourad Ogbi ◽  
Ha Won W Kim ◽  
Neal L Weintraub

Introduction: Abdominal aortic aneurysms (AAA) are characterized by inflammation and matrix metalloproteinase (MMP)-mediated degradation of extra cellular matrix proteins leading to aortic dilation and potentially rupture. Inflammatory chemokines that promote AAA are modulated by binding to the Duffy antigen receptor for chemokines (DARC), a non-signaling receptor expressed primarily on erythrocytes. Interestingly, African Americans exhibit reduced frequency of AAA, and the majority of African descendent individuals do not express DARC on their erythrocytes. Here, we tested the hypothesis that DARC gene deletion protects against the development of AAA. Methods: The induction of AAA was performed using both angiotensin II (AngII) infusion and calcium chloride (CaCl 2 ) application models. Eight week old LDLR knockout (KO, control) and LDLR KO/DARC KO mice were infused with AngII via osmotic mini-pumps for four weeks. For the CaCl 2 application model, twelve week old DARC KO and WT control mice underwent laparotomy and 0.5 mol/L CaCl 2 was applied to the infrarenal aorta. Aortic dilation and AAA formation was assessed using ultrasound, mice were then euthanized and tissues were harvested for analysis. Results: The aortic diameter of LDLR KO/DARC KO mice was significantly lower relative to control mice after AngII infusion (P=0.02). There was no difference in the pressor response to AngII between groups. Furthermore, IL-6 levels were significantly reduced in the aortas of LDLR KO/DARC KO mice compared to control mice (P=0.001). Expression of MCP-1, which has strong affinity for DARC, tended to be higher in aortas from LDLR KO/DARC KO mice compared to control (P=0.063). In contrast, plasma IL-6 levels were similar in both LDLR KO/DARC KO and control mice, while MCP-1 tended to be lower in the plasma of LDLR KO/DARC KO (P=0.07). DARC KO mice likewise exhibited a trend toward reduced aortic dilation in the CaCl 2 application model compared to controls (P=0.09). Conclusions: DARC KO mice are protected against AAA formation, perhaps through differential regulation of aortic chemokine trafficking. Understanding the mechanisms by which loss of DARC confers protection from AAA formation may be relevant to ethnic differences in susceptibility to AAA.

2021 ◽  
Author(s):  
Dien Ye ◽  
Deborah Howatt ◽  
Zhenyu Li ◽  
Alan Daugherty ◽  
Hong S. Lu ◽  
...  

Objective: Aortic ruptures are fatal consequences of aortic aneurysms with macrophage accumulation being a hallmark at the site of ruptures. Pyroptosis is critical in macrophage-mediated inflammation. This study determined effects of pyroptosis on aortic dilation and rupture using GSDMD deficient mice. Approach and Results: In an initial study, male Gsdmd+/+ and Gsdmd-/- mice in C57BL/6J background (8 to 10 weeks old) were infected with adeno-associated viral vectors encoding mouse PCSK9D377Y gain-of-function mutation and fed a Western diet to induce hypercholesterolemia. After two weeks of AAV infection, angiotensin II (AngII, 1,000 ng/kg/min) was infused. During the 4 weeks of AngII infusion, 5 of 13 Gsdmd+/+ mice died of aortic rupture, whereas no aortic rupture occurred in Gsdmd-/- mice. In surviving mice, no differences in either ascending or abdominal aortic dilation were observed between Gsdmd+/+ and Gsdmd-/- mice. To determine whether protection of GSDMD deficiency against aortic rupture is specific to AngII infusion, we subsequently examined aortic pathologies in mice administered beta-aminopropionitrile (BAPN). BAPN (0.5% wt/vol) was administered in drinking water to male Gsdmd+/+ and Gsdmd-/- mice (4 weeks old) for 4 weeks. Six of 13 Gsdmd+/+ mice died of aortic rupture, whereas no aortic rupture occurred in Gsdmd-/- mice. In mice survived, no differences of diameters in the ascending, arch, or abdominal aortic regions were observed between Gsdmd+/+ and Gsdmd-/- mice. Conclusions: GSDMD deficiency protects against AngII or BAPN-induced aortic ruptures in mice.


2018 ◽  
Vol 6 ◽  
pp. 2050313X1876130
Author(s):  
Zahira Zouizra ◽  
Soukaina Benbakh ◽  
Gaël Biaou ◽  
Drissi Boumzebra

Mycotic aortic aneurysms are exceedingly uncommon in infants and they have a high risk of rupture. Their surgical management is extremely challenging. We report a case of a 22-month-old girl who presented with abdominal pain and fever revealing a ruptured mycotic aneurysm of the infrarenal aorta. The surgical treatment consisted of a ligature of the proximal and distal ends of the aneurysm. Postoperative course was significant for hypertension. A year and a half follow-up showed no other complications. Limited data are available concerning our chosen technique, but the reported cases showed a good short-term outcome.


Author(s):  
Ron Layman ◽  
Samy Missoum ◽  
Jonathan Vande Geest

The local dilation of the infrarenal aorta, termed an abdominal aortic aneurysm (AAA), occurs over several years and may eventually lead to rupture, an event currently ranked the 15th leading cause of death in the United States [1, 2]. AAA can often remain quiescent and asymptomatic, making the diagnosis and treatment of AAA patients a clinical challenge. For patients whose AAAs dilate to a critical diameter there are two standard treatments: open surgical resection and endovascular repair (EVAR). EVAR involves inserting an endovascular graft into the aneurysm to prevent pressurization of the AAA cavity.


VASA ◽  
2003 ◽  
Vol 32 (4) ◽  
pp. 218-220 ◽  
Author(s):  
Papadimitriou ◽  
Tachtsi ◽  
Koutsias ◽  
Pitoulias ◽  
Mpompoti

The mycotic aneurysms of the infrarenal aorta (MAIA) are extremely rare and the associated morbidity and mortality is very high. The classification of infected aneurysms considers four types: a) true mycotic aneurysms, b) secondary mycotic aneurysms due to bacterial arteritis, c) infected preexisting abdominal aortic aneurysms and d) post-traumatic infected false aneurysms. The prognosis of true MAIA’s is better than the other forms of infected aneurysms. The standard treatment includes the resection of the aneurysm and infectious surrounding tissues and the restoration of the flow using ex situ (axillobifemoral) bypass or in situ replacement with autologous vein or a rifampicine-bonded graft. We present a case of mycotic aneurysm of the infrarenal aorta and a brief discussion of the alternative treatments from the relevant literature.


1997 ◽  
Vol 4 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Hardy Schumacher ◽  
Hans H. Eckstein ◽  
Friedrich Kallinowski ◽  
Jens Rainer Allenberg

Purpose: To evaluate the anatomic morphology of abdominal aortic aneurysms (AAAs) and compose a classification system to facilitate patient selection for endovascular graft (EVG) repair. Methods: Data on 242 consecutive AAA patients evaluated on a nonemergent basis in a 3.5-year period to July 1996 were prospectively entered into a registry. Patients were examined using sequential intravenous spiral computed tomographic angiography and intraarterial digital subtraction angiography. The data collected and analyzed included: diameters of the supra- and infrarenal aorta, aneurysm, aortoiliac bifurcation, and iliac arteries; lengths of the proximal neck, distal cuff, and aneurysm; degrees of iliac artery tortuosity; and occlusion of the visceral, renal, or iliac arteries. Results: The 242 aneurysms could be easily grouped into three distinctive categories related to the extent of the aneurysmal disease. Type I AAAs (11.2%) had nondilated, thrombus-free infrarenal (15 mm) necks and distal (10 mm) cuffs appropriate for EVG anchoring. In type II and its subgroups (72.3%), a sufficient proximal neck was present, but the aneurysm extended into the iliac arteries; 56% of these were eligible for a bifurcated endograft. In type III (16.5%), a sufficient proximal neck was missing, independent of distal involvement. In all, 51.7% were good EVG candidates based on AAA morphology. Taking into consideration relevant concomitant vascular diseases, proximal iliac kinking, and iliac, renal, or visceral occlusive disease, only 30.2% of the population were potential candidates for an efficient and secure EVG repair using the devices currently available. Conclusions: In contrast to classical open repair, detailed preoperative measurements are recommended for EVG planning. The use of liberal EVG indications may lead to a higher incidence of complications, whereas restrictive morphology-based selection criteria may offer excellent results.


2021 ◽  
pp. 157-163
Author(s):  
A. E. Zotikov ◽  
M. R. Khokonov ◽  
K. Kh. Eminov ◽  
A. M. Solovieva ◽  
A. V. Kozhanova ◽  
...  

Today, abdominal aortic aneurysm surgery is a fairly well-studied area of medicine. Nevertheless, some questions remain rather debatable. No clear criteria for giant aneurysms have been developed so far. The available foreign and domestic literature reports about 40 cases of surgical treatment of giant abdominal aortic aneurysms, 16 of which are cases of aneurysm rupture. Open surgery remains the method of choice in the treatment of giant aneurysms due to the pronounced technical difficulties of endovascular intervention. The authors present a case of successful surgical treatment of a giant aneurysm rupture in an elderly patient. The peculiarity of this patient's condition is the occurrence of aneurysm rupture after hospital admission. The patient refused surgical treatment for two years after aneurysm detection. On examination after admission, multispiral computed tomography revealed an aneurysm size of 101 mm. On the eve of surgery, pain syndrome in the left abdomen and tachycardia appeared. Aneurysm rupture was suspected and the patient was urgently admitted to the operating room. The surgery was performed under the conditions of machine reinfusion of autoblood. The patient underwent abdominal aortic aneurysm resection with linear prosthesis and retroperitoneal hematoma removal. The postoperative period had no peculiarities. On the 10th day after the operation the patient was discharged in satisfactory condition to the outpatient treatment. This clinical case demonstrates the possibility of successful surgical treatment of giant aneurysm rupture in elderly patients.


Author(s):  
Avinash Ayyalasomayajula ◽  
Bruce R. Simon ◽  
Jonathan P. Vande Geest

Abdominal aortic aneurysm (AAA) is a progressive dilation of the infrarenal aorta and results in a significant alteration in local hemodynamic environment [1]. While an aneurysmal diameter of 5.5cm is typically classified as being of high risk, recent studies have demonstrated that maximum wall stress could be a better indicator of an AAA rupture than maximum diameter [2]. The wall stress is greatly influenced by the blood pressure, aneurysm diameter, shape, wall thickness and the presence of thrombus. The work done by Finol et al. suggested that hemodynamic pressure variations have an insignificant effect on AAA wall stress and that primarily the shape of the aneurysm determines the stress distribution. They noted that for peak wall stress studies the static pressure conditions would suffice as the in vivo conditions. Wang et al have developed an isotropic hyperelastic constitutive model for the intraluminal thrombus (ILT). Such models have been used to study the stress distributions in patient specific AAAs [3, 4].


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas De Leo ◽  
Atlee Melillo ◽  
Jeremy Badach ◽  
Henry Miller ◽  
Andrew Lin ◽  
...  

Introduction: Abdominal aortic aneurysms (AAA) are responsible for over 150,000 deaths worldwide annually. Attempts at producing a reliable large-animal model of AAA have proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. Methods: A total of 9 male Yorkshire swine received periadventitial injections of type 1 collagenase (23.5 mg) and porcine pancreatic elastase (500 mg) into a 4 cm segment of infrarenal aorta. Aortic diameter growth was monitored at POD 7 and 14 using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal (treated) aorta was harvested for analysis, after gross measurement of aortic diameter under physiologic blood pressure. Sections of control and treated aorta were used to obtain tensile strength using a tensiometer. Additional segments of the aorta were collected for histopathological analysis (H&E, elastin, alpha smooth muscle actin). PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA for repeated measures, where appropriate. Results: Average percent growth of aortic diameter at POD 21 for treated segments was 27% +/- 16.5% versus 4.5% +/- 4% for control tissue. The average difference in aortic growth by subject, was 26.7% [14.6%-38.8%]; (p<0.001). Aortic medial thickness was decreased in treated tissue; 235 um +/- 208 um versus 645 um +/- 191 um (p<0.0001). Quantity of both medial elastin fibers, and vascular smooth muscles cells was decreased in treated tissue; 1.8% +/- 3.16%, compared to 9.9% +/- 6.85% (p<0.0001), and 24% +/- 6.8% versus 37.4% +/- 6.9%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa +/- 7 MPa versus 29.5 MPa +/- 10.7 MPa (p=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (p=0.002) Conclusion: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.


1997 ◽  
Vol 4 (2) ◽  
pp. 174-181 ◽  
Author(s):  
Matthew M. Thompson ◽  
Robert D. Sayers ◽  
Ahktar Nasim ◽  
Jonathan R. Boyle ◽  
Guy Fishwick ◽  
...  

Purpose: To describe a refined technique for aortomonoiliac endograft exclusion of abdominal aortic aneurysms (AAAs). Methods: A tapered aortomonoiliac graft was prepared from an 8-mm thin-walled expanded polytetrafluoroethylene tube graft predilated proximally to 35 mm and tapered distally to 15 mm. The proximal graft was sutured to a 5-cm-long, predilated Palmaz stent, which was mounted on a 30-mm balloon and backloaded into a 21F packaging sheath. With the patient under general anesthesia and both common femoral arteries exposed, the endograft was anchored in the infrarenal aorta and subsequently passed into one iliac system, where it was anastomosed to the iliac or femoral vessels. The contralateral common iliac artery was occluded, and an extra-anatomic, femorofemoral, or iliofemoral bypass grafting was performed. Results: Twenty of the 25 AAAs treated to date with this technique have been successful, with aneurysm exclusion achieved in 18 (2 minor distal endoleaks are scheduled for endovascular repair). The technical failures were analyzed, resulting in enhancements to the technique. Complications included 2 early (< 30 days) deaths, 1 case of minor embolization, 1 transient renal failure, 1 pulmonary embolus, and 1 wound infection. The only late complication was a graft infection localized to the groin. Conclusions: Aortomonoiliac endovascular aneurysm repair is effective in patients with AAAs involving the iliac arteries. Short-term results are acceptable, but long-term efficacy must be addressed before this procedure is widely adopted. Technical changes made in response to early learning curve problems have led to a safer, more reliable procedure.


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