scholarly journals Group V Secretory Phospholipase A2 Enhances the Progression of Angiotensin II–Induced Abdominal Aortic Aneurysms but Confers Protection against Angiotensin II–Induced Cardiac Fibrosis in ApoE-Deficient Mice

2012 ◽  
Vol 181 (3) ◽  
pp. 1088-1098 ◽  
Author(s):  
Boris B. Boyanovsky ◽  
William Bailey ◽  
Lauren Dixon ◽  
Preetha Shridas ◽  
Nancy R. Webb
Keyword(s):  
Angiotensin Ii ◽  
Phospholipase A2 ◽  
Cardiac Fibrosis ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Secretory Phospholipase A2 ◽  
Group V ◽  
Secretory Phospholipase ◽  
Abdominal Aortic ◽  
Deficient Mice

Abstract 919: Suppression of Abdominal Aortic Aneurysms in the Angiotensin II-infused ApoE Deficient Mice by Treatment with Chymase Inhibitor

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nao Inoue ◽  
Michiko Muramatsu ◽  
Denan Jin ◽  
Shinji Takai ◽  
Tetsuya Hayashi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Abdominal Aortic Aneurysms ◽  
Treated Group ◽  
Aortic Aneurysms ◽  
Aortic Diameter ◽  
Vehicle Group ◽  
Control Group ◽  
Abdominal Aortic ◽  
Chymase Inhibitor ◽  
Deficient Mice

Chymase promotes not only angiotensin II production but also matrix metalloproteinase (MMP)-9 activation, which have a critical role on development of abdominal aortic aneurysms (AAAs). The purpose of this study is to examine the effects of chymase inhibitor, NK3201, on the MMP-9 activity and development of AAA in the angiotensin II-induced apolipoprotein E (apoE)-deficient mice. Method: Angiotensin II (1000ng/kg/min) (vehicle group) or saline (control group) were infused into 16-week-old male apoE-deficient mice for 4 weeks. To examine the effect of chymase inhibition for AAA, we administered NK3201 (30mg/kg/day) to angiotensin II-infused group (NK3201-treated group) for the same period. At the end of angiotensin II infusion, we measured the diameters of suprarenal and infrarenal aorta. AAA severities were scored using the suprarenal aortic diameter/infrarenal aortic diameter ratio and presence of thrombus formation, i.e. under 2.0 was 0, from 2.0 to 2.5 was 1, from 2.5 to 3.0 was 2, over 3.0 was 3, and presence of thrombus was 4. We also determined the chymase and MMP-9 activities using total aorta. Results: The scores that reflected the progression and severity of AAA were increased in vehicle group compared with control group ( 2.35±0.30 vs. 0.27±0.12, p<0.01). This progression was inhibited in NK3201-treated group compared with vehicle group (1.13±0.35, p<0.05 vs. vehicle group). Chymase activity was significantly increased in vehicle group compared with control group. MMP-9 activity was also increased in vehicle group, however it was decreased significantly in NK3201-treated group.Discussion: We demonstrated that chymase inhibition could reduce AAA progression through inhibition of MMP-9 in angiotensin II-induced apoE-deficient mice. Chymase inhibitor might be a novel strategy for preventing AAAs.

Abstract 86: Intercellular Adhesion Molecule 1 Deficiency Attenuated Angiotensin II--Induced Abdominal Aortic Aneurysms in Apolipoprotein E--Deficient Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Haruhito A Uchida ◽  
Ryoko Umebayashi ◽  
Yuki Kakio ◽  
Kenichi Shikata ◽  
Hirofumi Makino
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Abdominal Aortic Aneurysms ◽  
Normal Diet ◽  
Aortic Aneurysms ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Abdominal Aortic ◽  
Deficient Mice ◽  
Mini Pump

Objective: Chronic infusion of angiotensin II (AngII) augments the development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Several studies have suggested that intercellular adhesion molecule 1 (ICAM-1) expression increases in association with AAA formation. The aim of the study was to define whether ICAM deficiency influenced AngII-induced AAA formation. Methods and Results: Apolipoprotein E deficient (apoE -/-) mice were cross-bred with ICAM-1 deficient mice. Male apoE -/- mice fed a normal diet and infused subcutaneously with saline or AngII (1,000 ng/kg/min) via osmotic mini pump for 1 week. AngII infusion increased aortic ICAM-1 protein. Male apoE -/- mice that were either ICAM-1 +/+ or -/- were fed a normal diet and infused subcutaneously with AngII (1,000 ng/kg/min) via osmotic mini pump for 4 weeks. Total ICAM-1 deficiency had no significant effect on body weight, total cholesterol concentrations, or systolic blood pressures prior to and during AngII infusion. AngII induced expansion of ex vivo maximal diameters of abdominal aortas was attenuated significantly in ICAM-1 deficient mice (ICAM-1 +/+, 1.78 ± 0.20 mm; ICAM-1 -/-, 1.07 ± 0.03 mm, P < 0.0001). ICAM-1 deficiency also reduced significantly the incidence of AngII-induced AAAs (ICAM-1 +/+, 76%; ICAM-1 -/-, 13%, P < 0.0001). Furthermore, bone-marrow transplantation was performed to develop chimeric mice that were ICAM-1 +/+ or -/- in donor cells and ICAM-1 +/+ or -/- in recipient cells. ICAM-1 deficiency in either donor or recipient cells had no effect on body weight, total cholesterol concentrations, or systolic blood pressure. Recipient ICAM-1 deficiency significantly attenuated the incidence of AngII-induced AAA formation (ICAM-1 +/+, 67%; ICAM-1 -/-, 19%, P = 0.0008). Furthermore, lack of ICAM-1 reduced AngII-induced aortic MMP-2 activation (P < 0.05). Conclusion: ICAM-1 deficiency attenuated AngII-induced AAAs in male apoE -/- mice.

Abstract 461: Cilnidipine Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms in Apolipoprotein E-deficient Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yuki Kakio ◽  
Haruhito A Uchida ◽  
Ryoko Umebayashi ◽  
Jun Wada
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Ex Vivo ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Osmotic Minipumps ◽  
Abdominal Aortic ◽  
Deficient Mice

Objective: Chronic infusion of angiotensin II (AngII) promotes development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Previous studies have shown that local inflammation and increased oxidative stress plays an important role on formation of AAAs. In addition, it is reported that voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by AngII in mice. Therefore, we hypothesized that cilnidipine, an N/L-type calcium channel blocker, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in mice. The purpose of this study was to evaluate whether cilnidipine influenced AngII-induced AAAs. Methods and Results: Male apolipoprotein E deficient mice (8-12 weeks old) were fed a normal laboratory diet. Mice were infused subcutaneously with either cilnidipine or vehicle by osmotic minipumps. Three days later, mice were also infused subcutaneously with either AngII (1,000 ng/kg/min, n = 14-16) or saline (n = 4) each by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure. Cilnidipine decreased blood pressure in AngII-infused mice, but had not effect during saline infusion. AngII infusion did not alter serum cholesterol concentrations. However, cilnidipine slightly decreased serumcholesterol concentrations in AngII-infused mice. Cilnidipine had no effect on body weights, heart rates, and urine total protein, but mildly restored plasma renin activity that were suppressed by AngII infusion. Cilnidipine did not affect ex vivo measurement of maximal diameter of abdominal aorta (1.04 ± 0.09 mm vs 1.11 ± 0.06 mm, n.s.) in saline infused mice. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas, but was attenuated by cilnidipine (1.79 ± 0.59 mm vs 1.26 ± 0.38 mm, P < 0.05). In addition, cilnidipine significantly reduced the incidence of AngII-induced AAAs (Cilnidipine: 38 %, Vehicle: 88 %; P < 0.05). Furthermore, gelatin zymography demonstrated that cilnidipine diminished AngII-induced increase in aortic MMP-9 protein abundance. Conclusion: Cilnidipine attenuated AngII-induced AAAs in male apolipoprotein E deficient mice.

scholarly journals Polychlorinated biphenyl 77 augments angiotensin II-induced atherosclerosis and abdominal aortic aneurysms in male apolipoprotein E deficient mice

2011 ◽  
Vol 257 (1) ◽  
pp. 148-154 ◽  
Author(s):  
Violeta Arsenescu ◽  
Razvan Arsenescu ◽  
Madhura Parulkar ◽  
Michael Karounos ◽  
Xuan Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Polychlorinated Biphenyl ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Deficient Mice

Abstract 104: Cilnidipine Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms in Apolipoprotein E-deficient Mice via Its Anti-oxidative Stress Effect

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Yuki Kakio ◽  
Haruhito A Uchida ◽  
Ryoko Umebayashi ◽  
Jun Wada
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Stress Effect ◽  
Osmotic Minipumps ◽  
Abdominal Aortic ◽  
Deficient Mice

Objective: Chronic angiotensin II (AngII) infusion promotes development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Previous studies have shown that local inflammation and increased oxidative stress plays an important role on formation of AAAs. In addition, voltage-dependent N-type Ca 2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by AngII in mice. Last year, we reported that cilnidipine, an N/L-type calcium channel blocker, attenuated AngII-induced AAAs in apolipoprotein E deficient mice. The purposed of this study was to determine the mechanism of cilnidipine reducing AngII-induced AAAs Methods and Results: Male apolipoprotein E deficient mice (8-12 weeks old) were fed a normal laboratory diet. Mice were infused subcutaneously with either cilnidipine or vehicle by osmotic minipumps. Three days later, mice were also infused subcutaneously with either AngII (1,000 ng/kg/min, n = 14-16) or saline (n = 4) by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure. Cilnidipine decreased blood pressure in AngII-infused mice, but had not effect during saline infusion. Cilnidipine mildly restored plasma renin activity that were suppressed by AngII infusion. Cilnidipine mildly decreased plasma aldosterone concentrations that were increased by AngII infusion. Cilnidipine significantly reduced the incidence of AngII-induced AAAs (cilnidipine: 38 %, Vehicle: 88 %; P < 0.05). Elastica van Gieson staining demonstrated degeneration of elastic lamina by AngII was suppressed by cilnidipine administration. Immunohistochemical staining of CD68 revealed that cilnidipine administration attenuated accumulation of CD68 positive macrophage by AngII. In addition, cilnidipine reduced oxidative stress by AngII in 8-hydroxy-2’-deoxyguanosine and 4-Hydroxy-2-nonenal staining. Conclusion: Cilnidipine attenuated AngII-induced AAAs in male apolipoprotein E deficient mice by its anti-inflammation and anti-oxidative stress effect.

Abstract 514: Cilostazol Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms Thorough Anti-inflammatory Effect in Apolipoprotein E-deficient Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ryoko Umebayashi ◽  
Haruhito A Uchida ◽  
Hirofumi Makino
Keyword(s):  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Mrna Expression ◽  
Experimental Studies ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Anti Inflammatory ◽  
Deficient Mice ◽  
Inflammatory Effect

Objective Chronic angiotensin II (AngII) infusion promotes development of abdominal aortic aneurysms (AAAs) in mice. Previous studies have shown that local inflammation plays an important role on formation of AAAs. Cilostazol, a phosphodiesterase-3 inhibitor with antiplatelet aggregation and vasodilatory effects, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in several experimental studies. The purpose of this study was to evaluate whether cilostazol influenced AngII-induced AAAs. Methods and Results Male apolipoprotein E deficient mice (8-12 weeks old) were fed with either normal diet or cilostazol-containing (0.1% wt/v) diet. After 1 week of cilostazol administration, mice were infused subcutaneously with either AngII (1,000 ng/kg/min, n = 16 -19) or saline (n = 5 - 6) by osmotic minipumps for 4 weeks. AngII equivalently increased systolic blood pressure, irrespective of cilostazol administration. Cilostazol had no effect on serum cholesterol concentrations, triglycerides, high-density lipoprotein-cholesterol, body weights, heart rates, and systolic blood pressures. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas that were attenuated by cilostazol administration (1.94 ± 0.16 mm vs 1.53 ± 0.17 mm, P < 0.05). Cilostazol diminished AngII-induced increase of aortic MMP-2 activity and ICAM-1 protein expression as determined by gelatin zymography and Western blot, respectively (P < 0.05, each). Aortic mRNA expression of inflammatory cytokines such as MCP-1, IL-1β, osteopontin, and COX-2 was reduced by cilostazol administration (P < 0.05). In vitro, TNF-α increased MCP-1, ICAM-1 and VCAM-1 mRNA expression in mouse aortic endothelial cells. These enhancements were decreased by incubation with cilostazol (P < 0.05). Conclusion Cilostazol attenuated AngII-induced AAAs thorough its anti-inflammatory effect in male apolipoprotein E deficient mice.

scholarly journals Cilostazol Attenuates Angiotensin II–Induced Abdominal Aortic Aneurysms but Not Atherosclerosis in Apolipoprotein E–Deficient Mice

2018 ◽  
Vol 38 (4) ◽  
pp. 903-912 ◽  
Author(s):  
Ryoko Umebayashi ◽  
Haruhito A. Uchida ◽  
Yuki Kakio ◽  
Venkateswaran Subramanian ◽  
Alan Daugherty ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Deficient Mice
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