Gonzalez-Guerra, AndrésRoche-Molina, MartaGarcía-Quintáns, NievesSánchez-Ramos, CristinaMartín-Pérez, DanielLytvyn, Mariyade Nicolás-Hernández, JavierRivera-Torres, JoséArroyo, Diego FSanz-Rosa, DavidBernal, Juan A2023-02-092023-02-092021-08-06http://hdl.handle.net/10668/18460The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/adeno associated virus (AAV)angiotensinogenatherosclerosiscardiovascular risk-factordisease modelelevated blood-pressureprehypertensionreninAnimalsAtherosclerosisBlood PressureDisease Models, AnimalHumansHypertensionMaleMice, Inbred C57BLresearch article34445154open access10.3390/ijms221684481422-0067PMC8395088https://www.mdpi.com/1422-0067/22/16/8448/pdf?version=1628237152https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395088/pdf