Prior renovascular hypertension does not predispose to atherosclerosis in mice

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Prior renovascular hypertension does not predispose to atherosclerosis in mice. / Mortensen, Martin Bødtker; Nilsson, Line; Larsen, Tore G; Espeseth, Eirild; Bek, Marie; Bjørklund, Martin M; Hagensen, Mette K; Wolff, Anne; Gunnersen, Stine; Füchtbauer, Ernst-Martin; Boedtkjer, Ebbe; Bentzon, Jacob F.

In: Atherosclerosis, Vol. 249, 06.2016, p. 157-63.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{d956e0eb418d453f8124c45d18868eaf,
title = "Prior renovascular hypertension does not predispose to atherosclerosis in mice",
abstract = "BACKGROUND: Hypertension is a major risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Although lowering blood pressure with antihypertensive drugs reduces the increased risk of ASCVD, residual increased risk still remains, suggesting that hypertension may cause chronic changes that promote atherosclerosis. Thus, we tested the hypothesis that hypertension increases the susceptibility to atherosclerosis in mice even after a period of re-established normotension.METHODS: We used the 2-kidney, 1-clip (2K1C) technique to induce angiotensin-driven renovascular hypertension, and overexpression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene to cause severe hypercholesterolemia and atherosclerosis.RESULTS: First, we performed 2K1C (n = 8) or sham surgery (n = 9) in PCSK9 transgenic mice before they were fed a high fat diet for 14 weeks. As expected, 2K1C did not affect cholesterol levels, but induced cardiac hypertrophy and significantly increased the atherosclerotic lesion area compared to sham mice (1.8 fold, p < 0.01). Next, we performed 2K1C (n = 13) or sham surgery (n = 14) in wild-type mice but removed the clipped/sham-operated kidney after 10 weeks to eliminate hypertension, and subsequently induced hypercholesterolemia by way of adeno-associated virus-mediated hepatic gene transfer of PCSK9 combined with high-fat diet. After 14 weeks of hypercholesterolemia, atherosclerotic lesion areas were not significantly different in mice with or without prior 2K1C hypertension (0.95 fold, p = 0.35).CONCLUSION: Renovascular hypertension in mice does not induce pro-atherogenic changes that persist beyond the hypertensive phase. These results indicate that hypertension only promotes atherogenesis when coinciding temporally with hypercholesterolemia.",
author = "Mortensen, {Martin B{\o}dtker} and Line Nilsson and Larsen, {Tore G} and Eirild Espeseth and Marie Bek and Bj{\o}rklund, {Martin M} and Hagensen, {Mette K} and Anne Wolff and Stine Gunnersen and Ernst-Martin F{\"u}chtbauer and Ebbe Boedtkjer and Bentzon, {Jacob F}",
note = "Copyright {\textcopyright} 2016 Elsevier Ireland Ltd. All rights reserved.",
year = "2016",
month = jun,
doi = "10.1016/j.atherosclerosis.2016.03.030",
language = "English",
volume = "249",
pages = "157--63",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd.",

}

RIS

TY - JOUR

T1 - Prior renovascular hypertension does not predispose to atherosclerosis in mice

AU - Mortensen, Martin Bødtker

AU - Nilsson, Line

AU - Larsen, Tore G

AU - Espeseth, Eirild

AU - Bek, Marie

AU - Bjørklund, Martin M

AU - Hagensen, Mette K

AU - Wolff, Anne

AU - Gunnersen, Stine

AU - Füchtbauer, Ernst-Martin

AU - Boedtkjer, Ebbe

AU - Bentzon, Jacob F

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2016/6

Y1 - 2016/6

N2 - BACKGROUND: Hypertension is a major risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Although lowering blood pressure with antihypertensive drugs reduces the increased risk of ASCVD, residual increased risk still remains, suggesting that hypertension may cause chronic changes that promote atherosclerosis. Thus, we tested the hypothesis that hypertension increases the susceptibility to atherosclerosis in mice even after a period of re-established normotension.METHODS: We used the 2-kidney, 1-clip (2K1C) technique to induce angiotensin-driven renovascular hypertension, and overexpression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene to cause severe hypercholesterolemia and atherosclerosis.RESULTS: First, we performed 2K1C (n = 8) or sham surgery (n = 9) in PCSK9 transgenic mice before they were fed a high fat diet for 14 weeks. As expected, 2K1C did not affect cholesterol levels, but induced cardiac hypertrophy and significantly increased the atherosclerotic lesion area compared to sham mice (1.8 fold, p < 0.01). Next, we performed 2K1C (n = 13) or sham surgery (n = 14) in wild-type mice but removed the clipped/sham-operated kidney after 10 weeks to eliminate hypertension, and subsequently induced hypercholesterolemia by way of adeno-associated virus-mediated hepatic gene transfer of PCSK9 combined with high-fat diet. After 14 weeks of hypercholesterolemia, atherosclerotic lesion areas were not significantly different in mice with or without prior 2K1C hypertension (0.95 fold, p = 0.35).CONCLUSION: Renovascular hypertension in mice does not induce pro-atherogenic changes that persist beyond the hypertensive phase. These results indicate that hypertension only promotes atherogenesis when coinciding temporally with hypercholesterolemia.

AB - BACKGROUND: Hypertension is a major risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Although lowering blood pressure with antihypertensive drugs reduces the increased risk of ASCVD, residual increased risk still remains, suggesting that hypertension may cause chronic changes that promote atherosclerosis. Thus, we tested the hypothesis that hypertension increases the susceptibility to atherosclerosis in mice even after a period of re-established normotension.METHODS: We used the 2-kidney, 1-clip (2K1C) technique to induce angiotensin-driven renovascular hypertension, and overexpression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene to cause severe hypercholesterolemia and atherosclerosis.RESULTS: First, we performed 2K1C (n = 8) or sham surgery (n = 9) in PCSK9 transgenic mice before they were fed a high fat diet for 14 weeks. As expected, 2K1C did not affect cholesterol levels, but induced cardiac hypertrophy and significantly increased the atherosclerotic lesion area compared to sham mice (1.8 fold, p < 0.01). Next, we performed 2K1C (n = 13) or sham surgery (n = 14) in wild-type mice but removed the clipped/sham-operated kidney after 10 weeks to eliminate hypertension, and subsequently induced hypercholesterolemia by way of adeno-associated virus-mediated hepatic gene transfer of PCSK9 combined with high-fat diet. After 14 weeks of hypercholesterolemia, atherosclerotic lesion areas were not significantly different in mice with or without prior 2K1C hypertension (0.95 fold, p = 0.35).CONCLUSION: Renovascular hypertension in mice does not induce pro-atherogenic changes that persist beyond the hypertensive phase. These results indicate that hypertension only promotes atherogenesis when coinciding temporally with hypercholesterolemia.

U2 - 10.1016/j.atherosclerosis.2016.03.030

DO - 10.1016/j.atherosclerosis.2016.03.030

M3 - Journal article

C2 - 27100924

VL - 249

SP - 157

EP - 163

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -