RT Journal Article
T1 Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease.
A1 Gonzalez-Guerra, Andrés
A1 Roche-Molina, Marta
A1 García-Quintáns, Nieves
A1 Sánchez-Ramos, Cristina
A1 Martín-Pérez, Daniel
A1 Lytvyn, Mariya
A1 de Nicolás-Hernández, Javier
A1 Rivera-Torres, José
A1 Arroyo, Diego F
A1 Sanz-Rosa, David
A1 Bernal, Juan A
K1 adeno associated virus (AAV)
K1 angiotensinogen
K1 atherosclerosis
K1 cardiovascular risk-factor
K1 disease model
K1 elevated blood-pressure
K1 prehypertension
K1 renin
AB 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 (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.
YR 2021
FD 2021-08-06
LK http://hdl.handle.net/10668/18460
UL http://hdl.handle.net/10668/18460
LA en
DS RISalud
RD Apr 7, 2025