The Effect of Nicotine and Tobacco on Aortic Matrix Metalloproteinases in the Production of Aortic Aneurysm.

BACKGROUND: Aortic aneurysms (AAs) are without effective pharmacologic therapy, in clinical usage, in part because of the limited understanding of factors leading to AA development.

OBJECTIVE: The objectives of this study were to examine the evidence that cigarette smoking induces AAs through altering matrix metalloproteinases (MMP) and the molecular biology/pharmacology that maybe involved in this effect.

METHODS: A systematic search was conducted to identify studies that examined the links between cigarette smoke, MMP and AAs.

RESULTS: Eleven studies were identified. There was consistency, between studies. They found that cigarette smoke, nicotine or tobacco products increased aortic dimension and the proportion of AAs. Nicotine and tobacco constituents induced MMPs: MMP-1, MMP-2, MMP-8, MMP-9 and MMP-12 but with different levels of consistency. The molecular mechanisms involved in the pathogenesis of cigarette-induced AA formation, ranked according to the consistency of evidence include JNK, AMPK-α2, Jak Stat, and mTOR/p70Sk and PTEN pathways.

CONCLUSION: Nicotine and tobacco constituents translate the exposure to cigarette smoke into increased MMP expression through various molecular mechanisms whose interruption can form the basis for pharmacologic management of AAs.