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
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Aging
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Animals
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Aorta, Abdominal
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Aortic Aneurysm, Abdominal/drug therapy*
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Disease Models, Animal
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Humans
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Muscle, Smooth, Vascular/metabolism*
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Oxidative Stress
2.Tuberculous Aneurysm of the Abdominal Aorta: Endovascular Repair Using Stent Grafts in Two Cases.
Wei Chiang LIU ; Byung Kook KWAK ; Kyo Nam KIM ; Soon Yong KIM ; Joung Joo WOO ; Dong Jin CHUNG ; Ju Hee HONG ; Ho Sung KIM ; Chang Jun LEE ; Hyung Jin SHIM
Korean Journal of Radiology 2000;1(4):215-218
Tuberculous aneurysm of the aorta is exceedingly rare. To date, the standard therapy for mycotic aneurysm of the abdominal aorta has been surgery involving in-situ graft placement or extra-anatomic bypass surgery followed by effective anti-tuberculous medication. Only recently has the use of a stent graft in the treat-ment of tuberculous aortic aneurysm been described in the literature. We report two cases in which a tuberculous aneurysm of the abdominal aorta was success-fully repaired using endovascular stent grafts. One case involved is a 42-year-old woman with a large suprarenal abdominal aortic aneurysm and a right psoas abscess, and the other, a 41-year-old man in whom an abdominal aortic aneurysm ruptured during surgical drainage of a psoas abscess.
Adult
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Aneurysm, Infected/drug therapy/radiography/*surgery
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Antitubercular Agents/therapeutic use
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Aortic Aneurysm, Abdominal/drug therapy/radiography/*surgery
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*Blood Vessel Prosthesis Implantation
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Case Report
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Female
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Human
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Male
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Psoas Abscess/surgery
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*Stents
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Tuberculosis, Cardiovascular/drug therapy/radiography/*surgery
4.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
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adverse effects
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Animals
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Aortic Aneurysm, Abdominal
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chemically induced
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drug therapy
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Apolipoproteins E
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genetics
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Bortezomib
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pharmacology
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Intercellular Adhesion Molecule-1
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metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NF-kappa B
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metabolism
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Phosphorylation
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Proteasome Inhibitors
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pharmacology
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Random Allocation
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Signal Transduction
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T-Lymphocytes
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cytology
5.Tanshinone IIA attenuates the development of elastase-induced abdominal aortic aneurysm of rat.
Tao SHANG ; Zhao LIU ; Min ZHOU ; Chang-jian LIU
Chinese Journal of Surgery 2012;50(10):923-927
OBJECTIVETo determine if tanshinone IIA (Tan IIA) can influence the development of elastase-induced experimental abdominal aortic aneurysms (AAAs).
METHODSTotally 36 male Sprague-Dawley rats were randomly distributed into three groups (12 in each group): Tan IIA group, control group, and sham group. Rats of Tan IIA and control groups underwent intra-aortic elastase perfusion to induce AAAs, while rats of sham-group were perfused with saline. Rats of Tan IIA-group received Tan IIA treatment (2 mg/d). The luminal diameter of the aneurysm at the segment with maximum diameter were measured pre-perfusion and on the 4 time point after perfusion. Systolic blood pressure was measured by tail-cuff technique. Aortic tissue samples were obtained on 24 days after perfusion and evaluated by RT-PCR, Western blot, immunohistochemistry and Miller's elastin-Van Gieson's (EVG) staining.
RESULTSTwenty-four days after perfusion, Tan IIA significantly reduced increased aortic size compared to control group ((0.210 ± 0.002) cm vs. (0.304 ± 0.004) cm, t = 78.858, P = 0.000) without affecting blood pressure (t = -1.237 to -1.221, P > 0.05). The over-expression of matrix metalloproteinases (MMP)-2/9 (t = 25.943, P = 0.000; t = 42.815, P = 0.000), monocyte chemotactic protein-1 (MCP-1) (t = 4.518, P = 0.000), inducible nitric oxide synthase (iNOS) (t = 17.685, P = 0.000) and the destruction of elastic fibers in aortic tissue of control group were significantly less than Tan IIA group (0.469 ± 0.040 vs. 0.230 ± 0.024, t = 17.944, P = 0.000).
CONCLUSIONTanshinone IIA attenuates the development of elastase-induced experimental AAAs possibly by down-regulating MMP-2/9, MCP-1 and iNOS expression.
Animals ; Aortic Aneurysm, Abdominal ; chemically induced ; drug therapy ; Chemokine CCL2 ; metabolism ; Disease Models, Animal ; Diterpenes, Abietane ; therapeutic use ; Elastic Tissue ; metabolism ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Pancreatic Elastase ; adverse effects ; Rats ; Rats, Sprague-Dawley