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

Thromb Haemost. 2020 Nov;120(11):1492-1504. doi: 10.1055/s-0040-1714352. Epub 2020 Aug 9.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Chemotaxis, Leukocyte
  • Coronary Disease / blood
  • Coronary Disease / genetics
  • Drug Evaluation, Preclinical
  • Endothelial Cells / pathology
  • Extracellular Traps / physiology
  • Genetic Predisposition to Disease
  • Lipids / blood
  • Lipids / physiology
  • Mice
  • Nitric Oxide / physiology
  • P-Selectin / physiology
  • Plaque, Atherosclerotic / metabolism
  • Platelet Adhesiveness
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Membrane Glycoproteins / physiology
  • Risk
  • von Willebrand Factor / physiology

Substances

  • Lipids
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • von Willebrand Factor
  • Nitric Oxide