Effect of Doxycycline on Atherosclerosis: From Bench to Bedside
Gaston A. Rodriguez-Granillo, Agustina Rodriguez-Granillo and Jose Milei
Affiliation: Department of Cardiovascular Imaging, Otamendi Hospital, Azcuenaga 870. C1115AAB. Buenos Aires, Argentina.
Keywords: Inflammation, coronary, metalloproteinase, remodeling, atherothrombosis, MMP inhibitor, apo E deficient mice, coro-nary artery disease, myocardial infarction, coronary atherosclerosis, MMPI, ECM remodeling, stromelysin-3, epilysin, VSMC, vasa vasorum, colla-genase-1, gelatinase-A, stromelysin-1, matrilysin, collagenase-2, gelatinase-B, stromelysin-2, metalloelastase, colla-genase-3, atherosclerosis, interleukin-6, fibrinogen, TIMP-1, ilomastat, solimastat, ncyclinide, S-3304, D-tryptophan, osteo-arthritis, CPA-926, SDD, Porphyromonas gingivalis, Chlamydia pneumoniae
Matrix metalloproteinases (MMPs) have a pivotal role in the natural history of atherosclerosis and its cardiovascular consequences. Non-selective MMP inhibition with doxycycline appears as a potential strategy to reduce the residual risk observed in patients already at intensive lipid lowering strategies. However, specific MMPs have different and even contradicting roles in the natural history of atherosclerosis, rendering broad spectrum MMP inhibition an important yet somewhat simplistic approach towards residual risk reduction in coronary atherosclerosis. Overall, the balance of non-selective MMP inhibition might shift to the favorable side in particular settings such as in acute coronary syndromes, where in addition to its potential plaque stabilization properties, doxycycline shows promise in preventing ischemia-reperfusion injury and left ventricular remodeling. Nevertheless, to date, most animal models used do not represent advanced coronary atherosclerosis seen in humans, and large and well-designed clinical studies are lacking. We discuss the available evidence and recent patents supporting the role of doxycycline in atherosclerosis.
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