Timing of clopidogrel loading dose on peripheral blood endothelial progenitor cells, SDF-1α and neointimal hyperplasia in carotid stenting

Article type: Research Article

Authors: Di Stolfo, Giuseppe^{a; 1; *} | Mastroianno, Sandra^{a; 1} | Ruggieri, Maurizio^b | Fontana, Andrea^c | Marinucci, Roberto^b | Copetti, Massimiliano^c | Minervini, Maria Marta^d | Savino, Lucia^d | Mastroianno, Mario^e | Savino, Maria^f | Pacilli, Michele Antonio^a | Di Mauro, Lazzaro^f | Potenza, Domenico Rosario^a | Cascavilla, Nicola^d | Paroni, Giovanni^b | Russo, Aldo^a

Affiliations: [a] Cardiology Unit, Cardiovascular Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy | [b] Vascular Surgery Unit, Cardiolovascular Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy | [c] Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy | [d] Hematology Unit, Onco-hematology Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy | [e] Unit of Information Systems and Innovation Research, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy | [f] Transfusion Medicine Unit and Laboratory of Clinical Chemistry, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy

Correspondence: [*] Corresponding author: Giuseppe Di Stolfo, MD, PhD, Cardiology Unit, Cardiovascular Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. Tel.: +39 3471 153419; Fax: +39 882 835463; E-mail: [email protected].

Note: [1] These two authors contributed equally to the study.

Abstract: BACKGROUND:Carotid stenting stimulates intimal proliferation through platelet and stem cell activation. OBJECTIVE:The aim of this study is to evaluate whether the administration before or after carotid stenting of clopidogrel loading dose may play a role on circulating endothelial progenitor cells, stromal cell-derived factor-1α (SDF-1α) and neointimal hyperplasia. METHODS:We recruited 13 patients (aged 74.52±7.23) with indication of carotid revascularization and in therapy with salicylic acid and statin. We blindly randomized them in two groups: pre-carotid angioplasty with stent (Pre-CAS group) receiving 300 mg of clopidogrel before stenting, and post-carotid angioplasty with stent (Post-CAS group) receiving 300 mg after stenting. At the admission, we valued endothelial progenitor cells, SDF-1α and prospectively we repeated blood samples and measured intima-media thickness to estimate neointimal hyperplasia on the stent at 3, 6 and 12 months. RESULTS:In the days following the CAS, we found a lower, statistically not significant, trend of endothelial progenitor cells in Pre-CAS group. The SDF-1α concentration tended to be lower at baseline in the pre-CAS group than in the post-CAS group and it did not show an increase in the observed time. On the contrary, in the Post-CAS group we observed a peak at six hours with a significant reduction (p < 0.001) at one day after stenting.The intima-media thickness was significantly lower in the Pre-CAS group than the Post-CAS group both at six months and 12 months after stenting. CONCLUSIONS:Pre-stenting clopidogrel loading dose leaded to short-time modification of endothelial progenitor cells and platelets and to long-term a minor neointimal hyperplasia.

Keywords: Endothelial progenitor cells, intima-media thickness, carotid stenting, clopidogrel therapy

DOI: 10.3233/CH-180429

Journal: Clinical Hemorheology and Microcirculation, vol. 72, no. 1, pp. 23-38, 2019