TY - JOUR 
A1 - González Guerra, Andrés
AU - Roche Molina, Marta
AU - García Quintáns, Nieves
AU - Sánchez Ramos, Cristina
AU - Martín Pérez, Daniel
AU - Lytvyn, Mariya
AU - Nicolás Hernández, Javier de
AU - Rivera Torres, José
AU - Arroyo, Diego F.
AU - Sanz Rosa, David
AU - Bernal, Juan Antonio
T1 - Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease
Y1 - 2021
SN - 1422-0067
UR - http://hdl.handle.net/11268/10563
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.
KW - Aterosclerosis
KW - Parvoviridae
KW - Prehipertensión
KW - Enfermedad cardiovascular
KW - Virus
LA - eng
ER -