1.Role of Vascular Aging in the Pathogenesis of Abdominal Aortic Aneurysm and Potential Therapeutic Targets.
Jian-Qiang WU ; Wei WANG ; Yue-Hong ZHENG
Acta Academiae Medicinae Sinicae 2021;43(6):962-968
Abdominal aortic aneurysm(AAA)is a common aortic degenerative disease in the elderly,and its incidence is gradually increasing with the aging of the population.There are no specific drugs available to delay the expansion of AAA.Once the aneurysm ruptures,the mortality will exceed 90%,which seriously threatens the life of patients.Given the high incidence of AAA in the elderly,this review discusses the role of vascular aging in the pathogenesis of AAA,involving chronic inflammation,oxidative stress,mitochondrial dysfunction,protein homeostasis imbalance,increased apoptosis and necrosis,extracellular matrix remodeling,nutritional sensing disorders,epigenetic changes,and increased pro-aging factors.Meanwhile,several potential aging-related drug targets of AAA are listed.This review provides new ideas for basic and translational medical research of AAA.
Aged
;
Aging
;
Animals
;
Aorta, Abdominal
;
Aortic Aneurysm, Abdominal/drug therapy*
;
Disease Models, Animal
;
Humans
;
Muscle, Smooth, Vascular/metabolism*
;
Oxidative Stress
3.Effect of Bortezomib on Angiotensin Ⅱ-induced Abdominal Aortic Aneurysm in ApoEMice.
Fangda LI ; Huihua LI ; Cui TIAN ; Hao NIE ; Yuehong ZHENG
Acta Academiae Medicinae Sinicae 2017;39(1):120-127
Objective To investigate the role of proteasome inhibitor bortezomib (BTZ) in inflammatory response in abdominal aortic aneurysm (AAA) formation induced by angiotensin Ⅱ (Ang Ⅱ). Methods Ang Ⅱ-induced ApoEmice AAA models were established. Forty male ApoEmice (8-10-week-old) were randomly and equally divided into four groups:Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group.HE staining,immunohistochemical staining,and flow cytometry were used to analyze the inflammatory response. Real-time quantitative polymerase chain reaction (qPCR) was used to analyze the mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1). Western blotting was used to analyze the activation of nuclear factor κB signaling (NF-κB). Results The mean maximum suprarenal aortic diameter (Dmax) of Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group were (1.00±0.01),(0.99±0.01),(1.50±0.13),and (1.20±0.04)mm,respectively (F=8.959,P=0.000). The Dmax of Ang Ⅱ group was significantly larger than those of Sham group (P=0.000) and Ang Ⅱ+BTZ group (P=0.015). The incidence of AAA in Ang Ⅱ group,Ang Ⅱ+BTZ group,and Sham group were 60%,17%,and 0,respectively. HE staining revealed that the abdominal aortic wall thickening was more severe in Ang Ⅱ group than in Sham group and Ang Ⅱ+BTZ group,similar with the infiltration of inflammatory cells. Immunohistochemical staining demonstrated that the CD3T lymphocyte count was significantly higher in Ang Ⅱ group than in Sham group (107.9±15.9 vs. 0,P=0.000) and Ang Ⅱ+BTZ group (107.9±15.9 vs. 0.8±0.5,P=0.000). Flow cytometry also demonstrated that the proportion of the CD3T lymphocytes of the Ang Ⅱ group [(13.50±0.69)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(10.40±0.78)%] at week 1 (t=3.009,P=0.040),and the proportion of the CD3T lymphocytes of the Ang Ⅱ group [(22.70±0.93)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(15.10±0.97)%] at week 4 (t=5.654,P=0.005). The qPCR analysis showed that the mRNA expression of ICAM-1 was significantly up-regulated in Ang Ⅱ group than in Sham group (1.93±0.54 vs. 1.00±0.15,P=0.011) and Ang Ⅱ+BTZ group (1.93±0.54 vs. 0.83±0.08,P=0.009). Western blot analysis showed a lower phosphorylation level of inhibitor of NF-κB in the Ang Ⅱ group compared with the Sham group or Ang Ⅱ+BTZ group,accompanied with an increased phosphorylation level of p65. Conclusion Proteasome inhibitor BTZ can attenuate AAA formation partially by regulating T lymphocytes infiltration through regulating the mRNA expression of ICAM-1 regulated by the activation of NF-κB signaling pathway.
Angiotensin II
;
adverse effects
;
Animals
;
Aortic Aneurysm, Abdominal
;
chemically induced
;
drug therapy
;
Apolipoproteins E
;
genetics
;
Bortezomib
;
pharmacology
;
Intercellular Adhesion Molecule-1
;
metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
NF-kappa B
;
metabolism
;
Phosphorylation
;
Proteasome Inhibitors
;
pharmacology
;
Random Allocation
;
Signal Transduction
;
T-Lymphocytes
;
cytology
4.Rescue Technique for Malposition Caused by Mislabeled Stent Graft in Thoracic Aneurysm
Hyuk Jae JUNG ; Bong Soo SON ; Do Hyung KIM ; Sang Su LEE
Vascular Specialist International 2017;33(4):170-173
The aim of this paper is to report a salvage treatment for malpositioned stent graft due to mislabeled product during thoracic endovascular aortic repair (TEVAR) in descending thoracic aneurysm (DTA). A 78-year-old male presented with 6.7×4.1 cm sized saccular DTA and 7.1×7.3 cm sized abdominal aortic aneurysm (AAA). DTA was initially treated by TEVAR and 2 months later AAA was treated by open aortic repair. Unfortunately, although the stent graft was correctly labeled for DTA, the actual size of product wrapped in a box was different contrary to our expectations. On completion angiography, proximal sealing zone showed no endoleak, however, celiac trunk and superior mesenteric artery (SMA) was found to be accidentally occluded. Through an emergent thoracotomy, distal part of stent graft was removed by cutting distal segment of stent graft and pulling out maneuver to restore blood flow. The completion angiography presented no endoleak, and celiac trunk and SMA were secured. Cutting distal segment of stent graft and pulling out maneuver is one of feasible rescue technique to maintain blood flow of occluded celiac trunk during TEVAR.
Aged
;
Aneurysm
;
Angiography
;
Aortic Aneurysm, Abdominal
;
Blood Vessel Prosthesis
;
Endoleak
;
Humans
;
Male
;
Mesenteric Artery, Superior
;
Salvage Therapy
;
Stents
;
Thoracotomy
6.Surgeon Custom-Made Iliac Branch Device to Salvage Hypogastric Artery during Endovascular Aneurysm Repair.
Young Eun PARK ; Jae Hoon LEE ; Woo Sung YUN ; Ki Hyuk PARK
Journal of Korean Medical Science 2014;29(12):1678-1683
Endovascular salvage of the hypogastric artery using iliac branch device (IBD) during endovascular aortic aneurysm repair (EVAR), offers less invasive alternative solution to surgery to prevent pelvic ischemia. We have performed the first Korean surgeon custom-made IBD for this purpose to overcome the limitation of unavailability of the devices in Korea. Four patients with abdominal aortic aneurysm with bilateral common iliac artery aneurysm (CIAA) were treated using custom-made IBDs from October 2013 to December 2013. IBD was created in back table before EVAR operation using TFLE Zenith iliac limb stent graft (Cook Inc.). Three V12 (Atrium, Inc.) one Viabahn (Gore, Inc.) were used for bridging between IBD and target hypogastric artery. With this modification of IBD procedure, exteriorize the guide wire without snare device is possible which offers another benefit in terms of reducing medical costs comparing to commercial IBD. All operations were successful without any device related complications or postoperative endoleaks. During the mean follow up of 3 months, all IBD were patent without clinical complications. Surgeon custom made IBD is feasible and useful to preserve pelvic perfusion especially in the situation of limited commercial IBD availability in many countries. Long-term follow-up is needed to evaluate stent graft patency and IBD-related complications.
Aged
;
Aortic Aneurysm, Abdominal/*surgery
;
*Blood Vessel Prosthesis
;
Endovascular Procedures/*instrumentation
;
Equipment Design
;
Equipment Failure Analysis
;
Female
;
Humans
;
Iliac Aneurysm/*surgery
;
Iliac Artery/*surgery
;
Male
;
Salvage Therapy/*instrumentation/methods
;
*Stents
7.Tissue Responses to Stent Grafts with Endo-Exo-Skeleton for Saccular Abdominal Aortic Aneurysms in a Canine Model.
Young Il KIM ; Young Ho CHOI ; Jin Wook CHUNG ; Hyo Cheol KIM ; Young Ho SO ; Hyun Beom KIM ; Seung Kee MIN ; Jae Hyung PARK
Korean Journal of Radiology 2014;15(5):622-629
OBJECTIVE: We evaluated the effect of close contact between the stent and the graft on the induction of endothelial covering on the stent graft placed over an aneurysm. MATERIALS AND METHODS: Saccular abdominal aortic aneurysms were made with Dacron patch in eight dogs. The stent graft consisted of an inner stent, a expanded polytetrafluoroethylene graft, and an outer stent. After sacrificing the animals, the aortas with an embedded stent graft were excised. The aortas were inspected grossly and evaluated microscopically. RESULTS: The animals were sacrificed at two (n = 3), six (n = 3), and eight months (n = 2) after endovascular repair. In two dogs, the aortic lumen was occluded at two months after the placement. On gross inspection of specimens from the other six dogs with a patent aortic lumen, stent grafts placed over the normal aortic wall were covered by glossy white neointima, whereas, stent grafts placed over the aneurysmal aortic wall were covered by brownish neointima. On microscopic inspection, stent grafts placed over the normal aortic wall were covered by thin neointima (0.27 +/- 0.05 mm, mean +/- standard deviation) with an endothelial layer, and stent grafts placed over the aneurysmal aortic wall were covered by thick neointima (0.62 +/- 0.17 mm) without any endothelial lining. Transgraft cell migration at the normal aortic wall was more active than that at the aneurysmal aortic wall. CONCLUSION: Close contact between the stent and the graft, which was achieved with stent grafts with endo-exo-skeleton, could not enhance endothelial covering on the stent graft placed over the aneurysms.
Animals
;
Aortic Aneurysm, Abdominal/pathology/*therapy
;
Blood Vessel Prosthesis Implantation
;
Disease Models, Animal
;
Dogs
;
Endothelium, Vascular/cytology/pathology
;
*Stents
;
Tomography, X-Ray Computed
8.Internal Iliac Artery Embolization during an Endovascular Aneurysm Repair with Detachable Interlock Microcoils.
Woo Chul KIM ; Yong Sun JEON ; Kee Chun HONG ; Jang Yong KIM ; Soon Gu CHO ; Jae Young PARK
Korean Journal of Radiology 2014;15(5):613-621
OBJECTIVE: The purpose of this study was to evaluate the effectiveness of detachable interlock microcoils for an embolization of the internal iliac artery during an endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: A retrospective review was conducted on 40 patients with aortic aneurysms, who had undergone an EVAR between January 2010 and March 2012. Among them, 16 patients were referred for embolization of the internal iliac artery for the prevention of type II endoleaks. Among 16 patients, 13 patients underwent embolization using detachable interlock microcoils during an EVAR. Computed tomographic angiographies and clinical examinations were performed during the follow-up period. Technical success, clinical outcome, and complications were reviewed. RESULTS: Internal iliac artery embolizations using detachable interlock microcoils were technically successful in all 13 patients, with no occurrence of procedure-related complications. Follow-up imaging was accomplished in the 13 cases. In all cases, type II endoleak was not observed with computed tomographic angiography during the median follow-up of 3 months (range, 1-27 months) and the median clinical follow-up of 12 months (range, 1-27 months). Two of 13 (15%) patients had symptoms of buttock pain, and one patient died due to underlying stomach cancer. No significant clinical symptoms such as bowel ischemia were observed. CONCLUSION: Internal iliac artery embolization during an EVAR using detachable interlock microcoils to prevent type II endoleaks appears safe and effective, although this should be further proven in a larger population.
Aged
;
Aged, 80 and over
;
Aortic Aneurysm, Abdominal/radiography/*therapy
;
Blood Vessel Prosthesis Implantation
;
Embolization, Therapeutic
;
Female
;
Follow-Up Studies
;
Humans
;
Iliac Artery/*surgery
;
Male
;
Middle Aged
;
Retrospective Studies
;
Tomography, X-Ray Computed
9.A Case of Angiographic Embolization of Aortoenteric Fistula Caused by Endovascular Stent Grafting for an Abdominal Aortic Aneurysm.
Kwang Hun KO ; Seul Young KIM ; Il Soon JUNG ; Kyu Seop KIM ; Hee Seok MOON ; Jae Kyu SEONG ; Hyun Yong JEONG
The Korean Journal of Gastroenterology 2013;61(4):230-233
Aortoenteric fistula (AEF) developed after treatment for an abdominal aortic aneurysm (AAA) is a rare but usually fatal complication. We report a rare case of AEF bleeding after endovascular stent grafting for AAA which was managed angiographically. An 81-year-old man presented with hematochezia and acute abdominal pain for 1 day ago. Four years ago, an aortic stent was implanted in the infrarenal aorta for AAA. Endoscopies were performed to evaluate the hematochezia. Evidence of gastrointestinal bleeding was observed, but a clear bleeding point was not detected on upper endoscopy and colonoscopy. Contrast-enhanced computed tomography performed subsequently showed that the bleeding point was located in the fourth portion of the duodenum as an AEF caused by an inflammatory process in the stent-graft. Intra-arterial angiography showed a massive contrast leakage into the bowel via a small fistula from around the aortic stent graft site. Embolization was successfully performed by injecting a mixture of glue and lipiodol into the AEF tract. The patient was discharged with no evidence of gastrointestinal bleeding after the embolization.
Aged, 80 and over
;
Angiography
;
Aortic Aneurysm, Abdominal/*therapy
;
Aortic Diseases/*etiology/radiography/therapy
;
Embolization, Therapeutic
;
Endoscopy, Gastrointestinal
;
Fistula/*etiology/radiography/therapy
;
Gastrointestinal Hemorrhage/therapy
;
Humans
;
Male
;
Stents/*adverse effects
;
Tomography, X-Ray Computed
10.Elastic fiber regeneration in vitro and in vivo for treatment of experimental abdominal aortic aneurysm.
Jiang XIONG ; Wei GUO ; Ren WEI ; Shang-wei ZUO ; Xiao-ping LIU ; Tao ZHANG
Chinese Medical Journal 2013;126(3):437-441
BACKGROUNDThe pathological characteristics of abdominal aortic aneurysm (AAA) involved the regression of extracellular matrix (ECM) in aortic walls, especially elastic structure in medial layer. As the major structural protein of aorta, elastin contributes to the extensibility and elastic recoil of the vessels. We hypothesized that overexpression of elastin in vessel walls might regenerate the elastic structure of ECM, restore the elastic structure of the aneurysmal wall, and eventually lead to a reduction of aortic diameters (ADs) in an experimental model of AAA.
METHODSTropoelastin (TE) of Sprague Dawley (SD) rat was synthesized by reverse transcription polymerase chain reaction and used to construct adneviral vectors containing elastin precursor protein (AdTE-GFP). Cultured vascular smooth muscle cells (VSMCs) from aortas of male SD rats were transfected with AdTE-GFP, AdGFP, adenoviral vector (AdNull), and phosphate buffered saline (PBS). Immunofluorescence staining was performed to determine the expression of elastin in transfected cells. The expression of elastic fibers in ECM of VSMCs transfected with AdTE-GFP were detected by fluorescence microscopy and transmission electron microscopy (TEM) at 1, 3, and 5 days following gene transfer. The AAA vessel walls were infused with AdTE-GFP or an empty AdNull, or PBS directly into the aneurysmal lumen. ADs of the aneurysms were compared in infused aortas. Formation of new elastic fibers in vivo was assessed by hematoxylin and eosin, and elastic von-Giesson staining. Recombinant elastin-GFP in vivo was identified by immunohistochemical staining.
RESULTSElastic fibers were increased both in ECM of VSMC and in vessel walls after gene transfer. Histological studies revealed that the AdTE-GFP-transduced aortas had elastic fiber regeneration in the aneurysmal walls. The AdTE-GFP-transduced aortas showed a decreased AD (23.04% ± 14.49%, P < 0.01) in AAA vessel walls.
CONCLUSIONSElastic fibers have been successfully overexpressed both in vitro and in a rat model of AAA by a technique of gene transfer. The overexpression of elastic fibers within the aneurysmal tissue appeared to reverse the aneurysm dilatation in this model.
Animals ; Aortic Aneurysm, Abdominal ; metabolism ; therapy ; Elastic Tissue ; metabolism ; Elastin ; genetics ; metabolism ; Fluorescent Antibody Technique ; Male ; Muscle, Smooth, Vascular ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tropoelastin ; genetics ; metabolism

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