OBJECTIVE: Aliskiren is the first commercially available, orally active, direct renin inhibitor approved to treat hypertension. The renin-angiotensin system has been shown to be a significant contributor to the development of hypercholesterolemia-induced atherosclerosis. The aim of this study was to evaluate the antiatherosclerotic and plaque stabilization effects of aliskiren alone and in combination with atorvastatin. METHODS: APOE*3Leiden.CETP mice (n = 14-17/group) were fed a western-type diet (containing 0.25% cholesterol) alone or were treated with either aliskiren (15 mg/kg per day), atorvastatin (3.6 mg/kg per day) or a combination of aliskiren and atorvastatin. Effects on SBP, total cholesterol, inflammation markers and atherosclerotic size and composition were assessed. RESULTS: Aliskiren reduced SBP (-19%, P < 0.001) and atorvastatin reduced total cholesterol (-24%, P < 0.001). Atherosclerotic lesion area was reduced by aliskiren (-40%, P < 0.01), atorvastatin (-61%, P < 0.001) and the combination treatment (-69%, P < 0.001). Aliskiren alone and together with atorvastatin decreased the number of T cells in the aortic root area (-60%, P < 0.01; -41%, P < 0.05), as well as macrophage (-64%, P < 0.001; -72%, P < 0.001) and necrotic area (-52%, P = 0.071; -84%, P < 0.001) in the lesion. Atorvastatin alone and together with aliskiren decreased monocyte adherence (-43%, P < 0.05 and -51%, P < 0.01) and monocyte chemoattractant protein-1 (both -36%, P < 0.01). The combination treatment decreased the number of lesions (-17%, P < 0.05) and E-selectin (-17%, P < 0.05). CONCLUSION: Aliskiren inhibited atherosclerosis development and improved plaque stability alone and in combination with atorvastatin, possibly via a mechanism involving T cells. These results suggest a potential benefit of using aliskiren in a clinical setting, particularly in combination with statin treatment.
OBJECTIVE:Aliskiren is the first commercially available, orally active, direct renin inhibitor approved to treat hypertension. The renin-angiotensin system has been shown to be a significant contributor to the development of hypercholesterolemia-induced atherosclerosis. The aim of this study was to evaluate the antiatherosclerotic and plaque stabilization effects of aliskiren alone and in combination with atorvastatin. METHODS:APOE*3Leiden.CETP mice (n = 14-17/group) were fed a western-type diet (containing 0.25% cholesterol) alone or were treated with either aliskiren (15 mg/kg per day), atorvastatin (3.6 mg/kg per day) or a combination of aliskiren and atorvastatin. Effects on SBP, total cholesterol, inflammation markers and atherosclerotic size and composition were assessed. RESULTS:Aliskiren reduced SBP (-19%, P < 0.001) and atorvastatin reduced total cholesterol (-24%, P < 0.001). Atherosclerotic lesion area was reduced by aliskiren (-40%, P < 0.01), atorvastatin (-61%, P < 0.001) and the combination treatment (-69%, P < 0.001). Aliskiren alone and together with atorvastatin decreased the number of T cells in the aortic root area (-60%, P < 0.01; -41%, P < 0.05), as well as macrophage (-64%, P < 0.001; -72%, P < 0.001) and necrotic area (-52%, P = 0.071; -84%, P < 0.001) in the lesion. Atorvastatin alone and together with aliskiren decreased monocyte adherence (-43%, P < 0.05 and -51%, P < 0.01) and monocyte chemoattractant protein-1 (both -36%, P < 0.01). The combination treatment decreased the number of lesions (-17%, P < 0.05) and E-selectin (-17%, P < 0.05). CONCLUSION:Aliskiren inhibited atherosclerosis development and improved plaque stability alone and in combination with atorvastatin, possibly via a mechanism involving T cells. These results suggest a potential benefit of using aliskiren in a clinical setting, particularly in combination with statin treatment.
Authors: Brandon Ason; José W A van der Hoorn; Joyce Chan; Edward Lee; Elsbet J Pieterman; Kathy Khanh Nguyen; Mei Di; Susan Shetterly; Jie Tang; Wen-Chen Yeh; Margrit Schwarz; J Wouter Jukema; Rob Scott; Scott M Wasserman; Hans M G Princen; Simon Jackson Journal: J Lipid Res Date: 2014-09-25 Impact factor: 5.922
Authors: Hong Yuan; Haiqiang Hu; Jindong Sun; Mingjuan Shi; Huamin Yu; Cairong Li; Y U Sun; Zhijian Yang; Robert M Hoffman Journal: In Vivo Date: 2018 Sep-Oct Impact factor: 2.155
Authors: Susan Kühnast; José W A van der Hoorn; Elsbet J Pieterman; Anita M van den Hoek; William J Sasiela; Viktoria Gusarova; Anusch Peyman; Hans-Ludwig Schäfer; Uwe Schwahn; J Wouter Jukema; Hans M G Princen Journal: J Lipid Res Date: 2014-08-19 Impact factor: 5.922
Authors: Hanna E Auvinen; Yanan Wang; Hans Princen; Johannes A Romijn; Louis M Havekes; Johannes W A Smit; Onno C Meijer; Nienke R Biermasz; Patrick C N Rensen; Alberto M Pereira Journal: PLoS One Date: 2013-05-22 Impact factor: 3.240