Reprogramming the Mitochondrion in Atherosclerosis: Targets for Vascular Protection

Area of Science:

• Cardiovascular research
• Mitochondrial biology
• Atherosclerosis pathogenesis

Background:

• Cardiovascular diseases (CVDs) are a leading global cause of death, often linked to premature events.
• Atherosclerosis (AS), a primary driver of CVDs, involves metabolic issues, vascular inflammation, and organelle dysfunction.
• Mitochondria are key regulators of vascular homeostasis, with dysfunction contributing to AS progression.

Purpose of the Study:

• To review mechanistic insights into mitochondrial dysfunction in atherosclerosis.
• To critically evaluate therapeutic strategies targeting mitochondrial reprogramming for vascular protection.

Main Methods:

• Synthesis of current mechanistic knowledge on mitochondrial dysfunction in AS.
• Appraisal of preclinical and translational therapeutic approaches for mitochondrial reprogramming.

Main Results:

• Mitochondrial dysfunction (impaired OXPHOS, ROS overproduction, mtDNA damage, altered dynamics, defective mitophagy) promotes endothelial dysfunction, VSMC switching, and macrophage polarization.
• Mitochondrial reprogramming strategies (enhancing biogenesis, dynamics, quality control) show promise in preclinical vascular injury models.

Conclusions:

• Restoring mitochondrial homeostasis via reprogramming is a novel therapeutic paradigm for AS.
• Interventions like small molecules (resveratrol, MitoQ), gene therapy, and nanodelivery systems are under investigation for vascular protection.