Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease

Area of Science:

• Cardiovascular Science
• Genetics
• Pharmacology

Background:

• The continuous relationship between blood pressure (BP) and cardiovascular events highlights the arbitrary nature of hypertension cut-offs.
• Even high-normal BP levels are associated with increased cardiovascular risk.
• Persistent BP elevation is hypothesized to promote atherosclerotic plaque development.

Purpose of the Study:

• To establish a causal link between persistent elevated BP and atherosclerotic plaque development.
• To develop and validate a novel mouse model for studying mild BP elevations.

Main Methods:

• Adeno-associated virus (AAV) vectors were engineered to deliver human renin and angiotensinogen genes.
• A single AAV injection induced sustained mild BP elevation in mice (130 ± 20 mmHg).
• Atherosclerotic lesions were quantified in ApoE mice with AAV-induced mild BP elevation compared to normotensive controls.

Main Results:

• AAV-mediated gene transfer successfully induced sustained mild systolic BP increase (p = 0.05).
• Mild BP elevation in ApoE mice resulted in a 10-fold increase in atherosclerotic lesions compared to controls.
• BP control with a calcium channel blocker attenuated atheroma plaque development.

Conclusions:

• Non-optimal blood pressure, even within a physiological range, significantly contributes to atherosclerosis development.
• This preclinical model demonstrates that mild BP elevation accelerates plaque formation.
• Earlier intervention for elevated BP may be crucial for preventing atherosclerosis-related morbidity and mortality.