Post-translational modifications orchestrate mTOR-driven cell death in cardiovascular disease

Area of Science:

• Biochemistry and Molecular Biology
• Cardiovascular Biology
• Cellular Physiology

Background:

• The mechanistic target of rapamycin (mTOR) pathway controls fundamental cellular processes like metabolism, growth, and cell death.
• Dysregulation of mTOR signaling, often influenced by post-translational modifications (PTMs), is implicated in cardiovascular diseases (CVDs).

Purpose of the Study:

• To review recent advances in understanding PTM-mediated control of mTOR signaling in cardiovascular pathophysiology.
• To highlight emerging therapeutic strategies targeting PTMs or the mTOR axis for CVDs.

Main Methods:

• Systematic review of current literature on mTOR signaling and PTMs in cardiovascular context.
• Analysis of PTMs (phosphorylation, ubiquitination, SUMOylation, etc.) affecting mTOR regulators and effectors.
• Examination of therapeutic interventions targeting PTMs and the mTOR pathway.

Main Results:

• PTMs fine-tune mTOR activity, influencing cell fate decisions (apoptosis, autophagy, pyroptosis, ferroptosis) during cardiovascular stress.
• Aberrant PTMs contribute to the pathogenesis of atherosclerosis, myocardial infarction, heart failure, and ischemia-reperfusion injury.
• Various therapeutic agents, including mTOR inhibitors and SUMOylation modulators, show preclinical or clinical promise.

Conclusions:

• Understanding PTM-mTOR interactions is crucial for elucidating cardiovascular pathophysiology.
• Targeting PTMs and the mTOR axis presents novel therapeutic avenues for cardiovascular medicine and precision therapies.