Simon W Rabkin1. 1. Department of Medicine, Division of Cardiology, University of British Columbia, Level 9 2775 Laurel St. Vancouver, B.C., Canada V5Z 1M9.. rabkin@mail.ubc.ca.
Abstract
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.
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.
Authors: Carine Poussin; Marco van der Toorn; Sophie Scheuner; Romain Piault; Athanasios Kondylis; Rebecca Savioz; Rémi Dulize; Dariusz Peric; Emmanuel Guedj; Fabio Maranzano; Celine Merg; Moran Morelli; Anne-Laure Egesipe; Stéphanie Johne; Shoaib Majeed; Claudius Pak; Thomas Schneider; Walter K Schlage; Nikolai V Ivanov; Manuel C Peitsch; Julia Hoeng Journal: Arch Toxicol Date: 2021-07-27 Impact factor: 5.153