Thromb Haemost 2020; 120(11): 1492-1504
DOI: 10.1055/s-0040-1714352
Review Article

Novel Approaches to Fine-Tune Therapeutic Targeting of Platelets in Atherosclerosis: A Critical Appraisal

Thorsten Kessler
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany
2  Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., Partner Site Munich Heart Alliance, Munich, Germany
,
Heribert Schunkert
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany
2  Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., Partner Site Munich Heart Alliance, Munich, Germany
,
2  Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., Partner Site Munich Heart Alliance, Munich, Germany
3  Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum der Universität, Ludwig-Maximilians-Universität, Partner Site Munich Heart Alliance, Munich, Germany
› Author Affiliations
Funding This study was funded by Deutsche Forschungsgemeinschaft (grants: SFB1123 A2; SFB1123 B2).

Abstract

The pathogenesis of atherosclerotic vascular disease is driven by a multitude of risk factors intertwining metabolic and inflammatory pathways. Increasing knowledge about platelet biology sheds light on how platelets take part in these processes from early to later stages of plaque development. Recent insights from experimental studies and mouse models substantiate platelets as initiators and amplifiers in atherogenic leukocyte recruitment. These studies are complemented by results from genetics studies shedding light on novel molecular mechanisms which provide an interesting prospect as novel targets. For instance, experimental studies provide further details how platelet-decorated von Willebrand factor tethered to activated endothelial cells plays a role in atherogenic monocyte recruitment. Novel aspects of platelets as atherogenic inductors of neutrophil extracellular traps and particularities in signaling pathways such as cyclic guanosine monophosphate and the inhibitory adaptor molecule SHB23/LNK associating platelets with atherogenesis are shared. In summary, it was our intention to balance insights from recent experimental data that support a plausible role for platelets in atherogenesis against a paucity of clinical evidence needed to validate this concept in humans.

Supplementary Material



Publication History

Received: 13 January 2020

Accepted: 10 June 2020

Publication Date:
09 August 2020 (online)

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