Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic...

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Translational Science

Background:

• Aortic stenosis (AS) and atherosclerosis are common cardiovascular diseases with shared clinical and molecular features.
• Effective pharmacological treatments for AS are limited, unlike for atherosclerosis.
• Investigating shared mechanisms may reveal therapeutic repositioning opportunities for AS.

Purpose of the Study:

• To review overlapping risk factors, pathological mechanisms, and potential therapeutic strategies for AS and atherosclerosis.
• To explore the potential for repurposing existing drug classes for AS management based on shared pathways.

Main Methods:

• Conducted a narrative review of studies published between 2005 and 2025.
• Included clinical trials, experimental models, and molecular studies focusing on shared aspects of AS and atherosclerosis.
• Analyzed common risk factors, molecular pathways (inflammation, oxidative stress, lipid accumulation, calcification), and signaling pathways (RAS, Notch).

Main Results:

• Identified shared risk factors: age, hypertension, hyperlipidemia, and diabetes.
• Highlighted common molecular mechanisms: chronic inflammation, endothelial dysfunction, oxidative stress, lipid accumulation, and calcific remodeling.
• Noted potential drug classes for repositioning: PCSK9 inhibitors, Lp(a) lowering therapies, anti-inflammatories, and immunomodulators.

Conclusions:

• The significant overlap in risk factors and molecular pathways between AS and atherosclerosis provides a strong rationale for therapeutic repositioning.
• Targeting shared molecular pathways could lead to novel strategies to slow AS progression.
• Repurposing drugs may improve therapeutic options and patient outcomes for aortic stenosis.