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University of Kentucky

Saha Cardiovascular Research Center Faculty Publications

Hypercholesterolemia

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Full-Text Articles in Medicine and Health Sciences

No Effect Of Hypercholesterolemia On Elastase-Induced Experimental Abdominal Aortic Aneurysm Progression, Toru Ikezoe, Takahiro Shoji, Jia Guo, Fanru Shen, Hong S. Lu, Alan Daugherty, Masao Nunokawa, Hiroshi Kubota, Masaaki Miyata, Baohui Xu, Ronald L. Dalman Sep 2021

No Effect Of Hypercholesterolemia On Elastase-Induced Experimental Abdominal Aortic Aneurysm Progression, Toru Ikezoe, Takahiro Shoji, Jia Guo, Fanru Shen, Hong S. Lu, Alan Daugherty, Masao Nunokawa, Hiroshi Kubota, Masaaki Miyata, Baohui Xu, Ronald L. Dalman

Saha Cardiovascular Research Center Faculty Publications

Objective: Epidemiological studies link hyperlipidemia with increased risk for abdominal aortic aneurysms (AAAs). However, the influence of lipid-lowering drugs statins on prevalence and progression of clinical and experimental AAAs varies between reports, engendering controversy on the association of hyperlipidemia with AAA disease. This study investigated the impact of hypercholesterolemia on elastase-induced experimental AAAs in mice. Methods: Both spontaneous (targeted deletion of apolipoprotein E) and induced mouse hypercholesterolemia models were employed. In male wild type (WT) C57BL/6J mice, hypercholesterolemia was induced via intraperitoneal injection of an adeno-associated virus (AAV) encoding a gain-of-function proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) followed by …


One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang May 2019

One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang

Saha Cardiovascular Research Center Faculty Publications

Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides in vivo, male low-density lipoprotein receptor (Ldlr) or apolipoprotein E (Apoe) deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in …


Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty Mar 2008

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …