Abstract Number: PB0008
Meeting: ISTH 2021 Congress
Theme: Arterial Thromboembolism » Atherosclerosis
Background: Thromboxane(TX)-dependent platelet activation, plays a key role in atherothrombosis. Incomplete suppression by ASA of urinary 11-dehydro-TXB2 excretion is predictive of cardiovascular events. TIMP1 is secreted by platelets. However, no data exist on the relationship between TIMP1 and TX dependent platelet activation.
Aims: To evaluate intraplatelet(i) and circulating(c)TIMP1 levels in diabetic(T2DM) and noT2DM patients receiving low dose ASA, and whether they may be associated with residual TX dependent platelet activation.
Methods: Thirty-nine patients (20 with and 19 without T2DM) were evaluated. All patients were treated with ASA(100mg). Twenty-four had metabolic syndrome(MS) and twenty had nonalcoholic fatty liver disease(NAFLD). Plasma and iTIMP1 was measured by ELISA. Urinary 11-dehydro-TXB2 was measured by mass-spectrometry. Each subject signed written informed consent, Protocol was approved (GR-2011-02350450).
Results: In the whole group of patients and in noT2DM patients, cTIMP1 and iTIMP1 correlated directly (p=0.039 and p<0.001) according with the hypothesis of platelets as major source of circulating TIMP1. cTIMP1 levels were comparable between T2DM and no T2DM patients(p=0.513). iTIMP1 were higher in T2DM(p=0.027). Patients with MS had higher levels of iTIMP1 in the whole group and in patients with and without T2DM(p<0.001; p=0.032 and p=0.009 respectively). Higher levels of iTIMP1 were found in patients with NAFLD both in the whole group and in patients with T2DM(p=0.030 and p=0.043). cTIMP1 was directly related to 11-dehydro-TXB2 in the whole group and in T2DM patients(p=0.006 and p=0.027)(figure) suggesting a role for TIMP-1 in residual TX-dependent platelet activation.
Correlation between circulating TIMP1 and urinary 11-dehydro-TXB2 in the patients with type 2 diabetes mellitus
Conclusions: In patients in treatment with ASA (I) higher iTIMP1 levels are associated with metabolic diseases (T2DM, MS and NAFLD); (II) iTIMP1 may be a major source of cTIMP1 and (III) cTIMP1 is directly related to urinary 11-dehydro-TXB2, suggesting a contribution of residual TX to TIMP1 release, which may further amplify platelet activation, or vice versa a role for TIMP1 as a determinant of TX-dependent platelet activation.
To cite this abstract in AMA style:
Simeone P, Tripaldi R, Liani R, Ciotti S, Cavalca V, Camera M, Tremoli E, Santilli F. Tissue Inhibitor of Metalloproteinases-1 (TIMP1) is Related to Residual Thromboxane Dependent Platelet Activation in Patients with Type 2 Diabetes Mellitus Receiving Low Dose Aspirin [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/tissue-inhibitor-of-metalloproteinases-1-timp1-is-related-to-residual-thromboxane-dependent-platelet-activation-in-patients-with-type-2-diabetes-mellitus-receiving-low-dose-aspirin/. Accessed August 16, 2022.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/tissue-inhibitor-of-metalloproteinases-1-timp1-is-related-to-residual-thromboxane-dependent-platelet-activation-in-patients-with-type-2-diabetes-mellitus-receiving-low-dose-aspirin/