González Guerra, AndrésRoche Molina, MartaGarcía Quintáns, NievesSánchez Ramos, CristinaMartín Pérez, DanielLytvyn, MariyaNicolás Hernández, Javier deRivera Torres, JoséArroyo, Diego F.Sanz Rosa, DavidBernal, Juan Antonio2022-01-142022-01-142021González-Guerra, A., Roche-Molina, M., García-Quintáns, N., Sánchez-Ramos, C., Martín-Pérez, D., Lytvyn, M., Nicolás-Hernández, J., Rivera-Torres, J., Arroyo, D. F., Sanz-Rosa, D., & Bernal, J. A. (2021). Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease. International Journal of Molecular Sciences, 22(16), 8448. https://doi.org/10.3390/IJMS221684481422-0067http://hdl.handle.net/11268/10563The 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 (1011 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/AterosclerosisParvoviridaePrehipertensiónjournal article10.3390/IJMS22168448open accessEnfermedad cardiovascularVirus