Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug...

Area of Science:

• Cardiovascular research
• Pharmacology
• Translational medicine

Background:

• Cardiovascular disease (CVD) is a leading global cause of death, with atherosclerosis being a primary concern.
• Developing novel pharmacotherapies for CVD is hindered by challenges in understanding underlying biological mechanisms.
• Current preclinical animal models often fail to accurately replicate human atherosclerosis pathobiology.

Purpose of the Study:

• To provide an overview of atherosclerotic drug mechanisms and modalities.
• To highlight recent preclinical models that enhance understanding of atherosclerosis.
• To propose model adaptations for developing effective CVD treatments.

Main Methods:

• Literature review of existing and emerging preclinical models for atherosclerosis.
• Analysis of drug discovery approaches and their limitations in CVD.
• Discussion of mechanisms and modalities of current and investigational atherosclerotic drugs.

Main Results:

• Preclinical animal models are crucial for evaluating pharmacological interventions, despite limitations.
• Recent models offer improved insights into atherosclerosis and its clinical consequences.
• A clear understanding of model advantages and limitations is essential for drug development.

Conclusions:

• Optimizing traditional drug discovery approaches and understanding biological mechanisms are key.
• There is a need for consensus on appropriate in vivo models that mimic human atherosclerosis.
• Adaptations to preclinical models can facilitate the development of novel and effective atherosclerosis treatments.