To the Editor: Dr Meier and colleagues1 discuss their findings in the context of a potential
association between the risk of AMI and bacterial infection with organisms
susceptible to tetracyclines (and quinolones), particularly C pneumoniae. We wish to emphasize an alternative explanation for these
intriguing observations.
Tetracyclines are now known to exhibit a wide range of nonantimicrobial
therapeutic properties. As recently reviewed2- 3
and confirmed in more than 30 laboratories around the United States and abroad,
these properties include the ability to inhibit expression, activation, and
extracellular activity of matrix metalloproteinases (MMPs), which represent
a family of enzymes that help mediate connective tissue breakdown in various
diseases, including periodontitis, osteoarthritis and rheumatoid arthritis,
osteoporosis, cancer invasion and metastasis, abdominal aortic aneurysms,
and atherosclerotic plaques. Tetracyclines also can suppress the production
of inflammatory mediators involved in many of these disorders, such as prostaglandin
E2, nitric oxide, interleukin 11β, tumor necrosis factor α,
and interleukin 6, and they can scavenge reactive oxygen metabolites such
as hypochlous acid, superoxide anion, and hydroxyl anion. By synthesizing
a series of nonantimicrobial analogs of tetracycline (chemically modified
tetracyclines), we and others have shown that the tetracyclines can inhibit
connective tissue breakdown by a mechanism(s) independent of their antibiotic
activity.2- 3 We recently
reported that both doxycycline and several nonantimicrobial chemically modified
tetracyclines inhibit the development of aortic aneurysms in rats, an effect
associated with suppressed MMP activity in the arterial wall.4