{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:15:44Z","timestamp":1777497344744,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CH"],"published-print":{"date-parts":[[2023,7,18]]},"abstract":"<jats:p>Circulating platelets are sometimes exposed to high shear rate environments due to vascular stenosis, and the effect of transiently elevated pathological high shear rates on platelet activation and aggregation function has not been clarified. The aim of this study was to investigate the effect of pathological high shear rate (8302s-1) exposure time (3.16-25.3\u200ams) on platelet activation and aggregation function. In addition, by adding active ingredients of antiplatelet drugs such as ASA (an active ingredient of aspirin), Ticagrelor, Tirofiban and GP1BA (platelet membrane protein GPIb inhibitor) in vitro, we studied TXA2, P2Y12-ADP, GPIIb\/IIIa-fibrinogen and GPIb \/IX\/V-vWF receptor pathways to determine platelet activation function mediated by pathological high shear rate. In this study, we designed a set of microfluidic chips with stenosis lengths of 0.5\u200amm, 1\u200amm, 2\u200amm, 3\u200amm, and 4\u200amm, all with 80% stenosis, to generate pathological high shear forces that can act at different times. The whole blood flowing through the microchannels was collected by perfusion of sodium citrate anticoagulated whole blood at a physiological arterial shear rate (1500 s-1), and the expression levels of platelet surface activation markers (P-selectin and GP IIb\/IIIa) and the degree of platelet aggregation were analyzed by flow cytometry; platelet aggregation patterns were observed by microscopic examination of blood smears. The results showed that shearing significantly increased platelet activation and aggregation levels compared to un-sheared whole blood, and the activation and aggregation levels increased with increasing duration of pathological high shear rate. In vitro inhibition studies showed that ASA barely inhibited the expression of P-selectin and PAC-1 on the platelet surface; Ticagrelor effectively inhibited the expression of both P-selectin and PAC-1; Tirofiban significantly inhibited the expression of PAC-1 on the platelet surface and slightly inhibited the expression of P-selectin; GP1BA significantly inhibited the expression of both. Our results suggest that transient pathological high shear rate (8302s-1) exposure can induce platelet activation in a time-dependent manner; however, the mechanism is more complex and may be due to the following reasons: transient elevated pathological high shear rate activates platelets through the GPIb\/IX\/V-vWF receptor pathway, and after platelet activation, its surface membrane protein GPIIb\/IIIa receptors activate platelets through fibrinogen to form platelet-platelet aggregates, and further activation of active substances such as ADP and TXA2 released by platelet alpha particles, which contribute to the formation of irreversible platelet aggregation.<\/jats:p>","DOI":"10.3233\/ch-221567","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T11:49:21Z","timestamp":1681213761000},"page":"125-139","source":"Crossref","is-referenced-by-count":12,"title":["Effect of pathological high shear exposure time on platelet activation and aggregation"],"prefix":"10.1177","volume":"84","author":[{"given":"Tiancong","family":"Zhang","sequence":"first","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Huang","sequence":"additional","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Gao","sequence":"additional","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Chen","sequence":"additional","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanrong","family":"Huan","sequence":"additional","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"He","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/CH-221567_ref1","doi-asserted-by":"publisher","first-page":"00141","DOI":"10.3389\/fcvm.2019.00141","article-title":"Shear-Dependent Platelet Aggregation: Mechanisms and Therapeutic Opportunities","volume":"6","author":"Rana","year":"2019","journal-title":"Front Cardiovasc Med"},{"issue":"6","key":"10.3233\/CH-221567_ref2","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1161\/01.cir.80.6.1726","article-title":"Intimal fibromuscular hyperplasia at the venous anastomosis of PTFE grafts in hemodialysis patients","volume":"80","author":"Swedberg","year":"1989","journal-title":"Clinical, immunocytochemical, light and electron microscopic assessment. 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