Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijms22168448
Keywords
renin; angiotensinogen; elevated blood-pressure; prehypertension; atherosclerosis; disease model; adeno associated virus (AAV); cardiovascular risk-factor
Funding
- Ministry of Science and Innovation [BFU2016-75144-R, PID2020-116935RB-I00]
- Universidad Europea de Madrid [2016/UEM20]
- Instituto de Salud Carlos III (ISCiii)
- Ministry of Science and Innovation
- Pro CNIC Foundation
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Elevated blood pressure, even within a physiological range, may contribute to atherosclerotic plaque development, as demonstrated in a new mouse model using AAV gene transfer technology.
The continuous relationship between blood pressure (BP) and cardiovascular events makes the distinction between elevated BP and hypertension based on arbitrary cut-off values for BP. Even mild BP elevations manifesting as high-normal BP have been associated with cardiovascular risk. We hypothesize that persistent elevated BP increases atherosclerotic plaque development. To evaluate this causal link, we developed a new mouse model of elevated BP based on adeno-associated virus (AAV) gene transfer. We constructed AAV vectors to support transfer of the hRenin and hAngiotensinogen genes. A single injection of AAV-Ren/Ang (10(11) total viral particles) induced sustained systolic BP increase (130 +/- 20 mmHg, vs. 110 +/- 15 mmHg in controls; p = 0.05). In ApoE(-/-) mice, AAV-induced mild BP elevation caused larger atherosclerotic lesions evaluated by histology (10-fold increase vs. normotensive controls). In this preclinical model, atheroma plaques development was attenuated by BP control with a calcium channel blocker, indicating that a small increase in BP within a physiological range has a substantial impact on plaque development in a preclinical model of atherosclerosis. These data support that non-optimal BP represents a risk for atherosclerosis development. Earlier intervention in elevated BP may prevent or delay morbidity and mortality associated with atherosclerosis.
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