Activation of AMP-activated protein kinase α2 by nicotine instigates formation of abdominal aortic aneurysms in mice in vivo
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Summary
This summary is machine-generated.Smoking, specifically nicotine, causes abdominal aortic aneurysms (AAA) by activating AMPK-α2 in vascular cells, leading to MMP2 expression. This study establishes a direct link between smoking and AAA development in vivo.
Area Of Science
- Cardiovascular Biology
- Molecular Medicine
- Vascular Biology
Background
- Smoking is the sole modifiable risk factor for abdominal aortic aneurysm (AAA).
- The precise mechanism linking cigarette smoke to AAA pathogenesis remains unclear.
- Abdominal aortic aneurysms are a significant cause of morbidity and mortality.
Purpose Of The Study
- To establish a causative link between smoking and abdominal aortic aneurysm (AAA) development in vivo.
- To elucidate the molecular mechanisms by which smoking contributes to AAA pathogenesis.
- To investigate the role of AMP-activated kinase (AMPK) in mediating smoking-induced AAA.
Main Methods
- Utilized apolipoprotein E (apoE) knockout mice and mice deficient in both apoE and AMPK subunits (Apoe(-/-); Prkaa1(-/-) and Apoe(-/-); Prkaa2(-/-)).
- Administered acute infusions of angiotensin II (AngII) or nicotine to induce AAA.
- Examined the activation of AMPK-α2, phosphorylation of activator protein 2α (AP-2α), and matrix metallopeptidase 2 (MMP2) gene expression in cultured vascular smooth muscle cells (VSMCs).
Main Results
- Nicotine and AngII markedly increased AAA incidence in Apoe(-/-) and Apoe(-/-); Prkaa1(-/-) mice.
- Genetic deletion of AMPK-α2 in Apoe(-/-); Prkaa2(-/-) mice completely abolished nicotine- or AngII-induced AAA.
- Nicotine and AngII activated AMPK-α2 in VSMCs, leading to AP-2α phosphorylation and subsequent MMP2 gene expression.
Conclusions
- Smoking, via nicotine, directly instigates abdominal aortic aneurysms (AAA) in vivo.
- The mechanism involves AMPK-α2 activation in vascular smooth muscle cells.
- This activation leads to AP-2α phosphorylation and MMP2 expression, promoting AAA development.