MMP-2, MMP-9, and TIMP-4 and Response to Aspirin in Diabetic and Nondiabetic Patients with Stable Coronary Artery Disease: A Pilot Study

Abstract EN

Background.

High on-aspirin treatment platelets reactivity (HPR) is a significant problem in long-term secondary prevention of cardiovascular events.

We hypothesize that imbalance between platelets MMPs/TIMPs results in cardiovascular disorders.

We also explored whether chronically elevated blood glucose affects MMP-2/TIMP-4 release from platelets.

Materials and Methods.

Seventy patients with stable coronary artery disease, supplemented with aspirin, participated in this pilot study.

The presence of HPR and/or diabetes mellitus was considered as the differentiating factor.

Light aggregometry, impedance aggregometry, and ELISA tests for TXB2, MMP-2, MMP-9, and TIMP-4 were performed in serum, plasma, platelet-rich plasma, and platelets-poor plasma, as appropriate.

Results.

Aspirin-HPR did not affect plasma MMP-2, MMP-9, and TIMP-4.

Arachidonic acid-induced aggregation of platelets from aspirin-HPR patients did not lead to increased release of MMP-2, MMP-9, and TIMP-4.

Studying patients at the lowest TXB2 serum concentration quartile revealed that high concentration of plasma TIMP-4 and TIMP-4 negatively correlated with TXB2 and platelet aggregation.

Diabetics showed an increased plasma MMP-2 as well as an increased MMP-2 in supernatants after platelet aggregation.

However, diabetes mellitus did not affect MMP-9 and TIMP-4.

Conclusion.

Aspirin-HPR did not affect the translocation and release of MMPs and TIMP-4 from platelets.

TIMP-4 may serve as a marker of TXA2-mediated platelet aggregation.

Chronically elevated plasma glucose increases plasma MMP-2, and HPR potentiates this phenomenon.