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

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.

A potential key mechanism in ascending aortic aneurysm development: Detection of a linear relationship between MMP-14/TIMP-2 ratio and active MMP-2

“…A previous study showed that chronically elevated plasma glucose increases plasma MMP-2 [31]. We were unable to demonstrate any association between MMP levels and the presence of diabetes mellitus in aortic tissue.…”

<p>Effects of functionalized silver nanoparticles on aggregation of human blood platelets</p>

“…Moreover, MMP-2 is involved in the modification of platelet glycoprotein α IIb β 3 resulting in enhanced platelet adhesion and aggregation 48,49,52. MMP-1 was also indicated to associate with the α IIb β 3 integrin, as suggested by Galt et al, 2002 52. It has been shown that MMP-2 contributed to platelets stimulation and aggregation by non-ADP and non-TXA 2 pathway 51,53…”

“…These MMPs rapidly relocate from granule structures inside the platelet to the plasma membrane of activated platelets and enhance P-selectin expression, platelet procoagulant activity, and thrombus formation 48–51. Moreover, MMP-2 is involved in the modification of platelet glycoprotein α IIb β 3 resulting in enhanced platelet adhesion and aggregation 48,49,52. MMP-1 was also indicated to associate with the α IIb β 3 integrin, as suggested by Galt et al, 2002 52.…”

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway

“…Chronic hypoxia (CH) is a condition where the partial pressure of oxygen in the blood is too low to saturate hemoglobin, which may be due to various reasons, including the decrease in the amount of breathable oxygen owing to a reduced barometric pressure [1], often encountered in pilots, mountain climbers, and people living at high altitudes. People inhabiting high altitudes are considered to be exposed to CH and show excessive erythrocytosis and hypoxemia [2,3].…”