Official websites use. Share sensitive information only on official, secure websites. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. High on-aspirin treatment platelets reactivity HPR is a significant problem in long-term secondary prevention of cardiovascular events.
Seventy patients with stable coronary artery disease, supplemented with aspirin, participated in this pilot study. Diabetes mellitus DM is one of the major risk factors for the development of cardiovascular disease and a higher mortality [ 1 ]. It has been reported that patients with DM type 2 and no previous history of coronary artery disease CAD have similar risk for cardiac events to patients with prior myocardial infarction [ 2 ]. Apart from traditional risk factors for the development of cardiovascular events in diabetes subjects, nowadays a lot of attention is payed to nontraditional risk factors including haematological and thrombogenic factors.
Atherothrombosis, defined as the formation of a thrombus on atherosclerotic plaque, is the leading cause of acute cardiovascular events [ 3 ]. Going further, it is well documented that hyperglycemia increases the expression and activity of matrix metalloproteinases MMPs in vascular macrophages and endothelial cells; hence it facilitates vascular remodeling and cardiovascular complications [ 4 ]. Matrix metalloproteinases are ubiquitous in the family of calcium-dependent zinc-containing endopeptidases that are mainly involved in the degradation and remodeling of extracellular matrix of the tissues.
They are expressed at low level in normal adult tissue turnovers such as reproduction [ 5 , 6 ], development [ 7 ], tissue repair [ 8 ], or immune response [ 9 , 10 ] and are upregulated during pathological processes including inflammation [ 11 ], autoimmune diseases [ 12 ], neurogenerative disorders [ 13 ], tumor invasion and metastasis [ 14 , 15 ], and heart injury [ 16 ].
Broad substrate specificities and strict regulation of their expression, activation, and inhibition levels contribute to maintenance of tissue homeostasis. The activity of MMPs is regulated mostly by the endogenous tissue inhibitors of metalloproteinases TIMPs , which bind to the active site of MMPs and block access to extracellular matrix substrates [ 17 , 18 ].
