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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

P. Simeone1, R. Tripaldi1, R. Liani1, S. Ciotti1, V. Cavalca2, M. Camera2, E. Tremoli2, F. Santilli1

1Department of Medicine and Aging, Center for Advanced Studies and Technology (CAST), University ‘G. d'Annunzio‘ of Chieti-Pescara, Chieti, Italy, 2Monzino Cardiology Center, IRCCS, Milan, Italy

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.

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