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

Author:

Yin Xiujie,Abudupataer Mieradilijiang,Ming Yang,Xiang Bitao,Lai Hao,Wang Chunsheng,Li Jun,Zhu KaiORCID

Abstract

Abstract: The occurrence and development of aortic aneurysms are accompanied by senescence of human aortic smooth muscle cells (HASMCs). Because the mechanism of HASMC senescence has not been fully elucidated, the efficacy of various antisenescence treatments varies. Decreased nicotinamide adenine dinucleotide (NAD+) levels are one of the mechanisms of cell senescence, and there is a lack of evidence on whether increasing NAD+ levels could alleviate HASMC senescence and further retard the progression of aortic aneurysms. We constructed an HASMC-based organ-on-a-chip microphysiological model. RNA sequencing was performed on cell samples from the vehicle control and angiotensin II groups to explore biological differences. We detected cellular senescence markers and NAD+ levels in HASMC-based organ-on-a-chip. Subsequently, we pretreated HASMC using the synthetic precursor of NAD+, nicotinamide mononucleotide, and angiotensin II treatment, and used rhythmic stretching to investigate whether nicotinamide mononucleotide could delay HASMC senescence. The HASMC-based organ-on-a-chip model can simulate the biomechanical microenvironment of HASMCs in vivo, and the use of angiotensin II in the model replicated senescence in HASMCs. The senescence of HASMCs was accompanied by downregulation of the expression level of nicotinamide phosphoribosyltransferase and NAD+. Pretreatment with nicotinamide mononucleotide significantly increased the NAD+ level and alleviated the senescence of HASMCs, but did not change the expression level of nicotinamide phosphoribosyltransferase. Our study provides a complementary research platform between traditional cell culture and animal experiments to explore HASMC senescence in aortic aneurysms. Furthermore, it provides evidence for NAD+ boosting therapy in the clinical treatment of aortic aneurysms.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Pharmacology

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