Nicotinamide Mononucleotide Alleviates Angiotensin II-Induced Human Aortic Smooth Muscle Cell Senescence in a...

Area of Science:

• Cardiovascular Biology
• Cellular Senescence
• Biomedical Engineering

Background:

• Aortic aneurysms are linked to human aortic smooth muscle cell (HASMC) senescence.
• Mechanisms of HASMC senescence are not fully understood, limiting treatment efficacy.
• Decreased nicotinamide adenine dinucleotide (NAD+) levels are implicated in cell senescence.

Purpose of the Study:

• To investigate if increasing NAD+ levels can alleviate HASMC senescence.
• To explore the potential of NAD+ boosting to retard aortic aneurysm progression.
• To establish an organ-on-a-chip model for studying HASMC senescence.

Main Methods:

• Developed an HASMC-based organ-on-a-chip microphysiological model.
• Used angiotensin II to induce HASMC senescence and RNA sequencing to analyze biological differences.
• Pretreated HASMCs with nicotinamide mononucleotide (a NAD+ precursor) to assess its effect on senescence.

Main Results:

• The organ-on-a-chip model successfully replicated in vivo biomechanical conditions and induced HASMC senescence.
• HASMC senescence correlated with reduced nicotinamide phosphoribosyltransferase and NAD+ levels.
• Nicotinamide mononucleotide pretreatment increased NAD+ levels and significantly alleviated HASMC senescence.

Conclusions:

• The HASMC organ-on-a-chip platform serves as a valuable research tool bridging cell culture and animal models.
• Findings provide evidence that NAD+ levels play a crucial role in HASMC senescence.
• NAD+ boosting therapy shows promise for clinical treatment of aortic aneurysms.