Circulating platelet-progenitor cell coaggregate formation is increased in patients with acute coronary syndromes and augments recruitment of CD34+ cells in the ischaemic microcirculation

Eur Heart J. 2013 Aug;34(32):2548-56. doi: 10.1093/eurheartj/eht131. Epub 2013 Apr 17.

Abstract

Aims: The aim of the present study was to evaluate the levels of platelet interaction with circulating CD34+ cells in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS) and to study the functional consequence of coaggregates formation in vitro and in vivo.

Methods and results: Platelet binding to circulating progenitor cells was defined by the presence of the platelet-specific marker glycoprotein Ib (CD42b) on the surface of CD34+ cells using flow cytometry. The percentage of CD34+/CD42b+ cell coaggregates was increased in patients with ACS (n = 162), and especially in patients with ST-elevation myocardial infarction (STEMI) (n = 44), compared with patients with SAP (n = 116; P < 0.001). In the ANCOVA analysis, platelet/CD34+ cell coaggregates were independently increased in ACS after adjustment for possible confounders. In a subgroup of our cohort, we also evaluated the levels of CD34+/CD133+/CD42b+ cell coaggregates, which were also significantly increased in ACS, and especially in STEMI (P < 0.05). Platelet/CD34+ cell coaggregates formation correlated with platelet activation (P = 0.001). In a prospective pilot study of patients with AMI (n = 40) using cardiac MRI, patients with increased baseline platelet/CD34+ cell coaggregates presented with a less myocardial infarct size and better left ventricular function at a 3-month follow-up compared with patients with lower coaggregates (P < 0.05 for all). The adhesion of platelet/CD34+ cell coaggregates onto the extracellular matrix and to endothelial monolayer was enhanced compared with CD34+ under high shear rates in vitro (P < 0.05) and within the microcirculation in mice after ischaemia/reperfusion injury as assessed by intravital microscopy (P < 0.05).

Conclusions: These findings imply that circulating platelet/CD34+ cell coaggregate levels are increased in ACS, especially in STEMI, which may be a novel mechanism of domiciliation of CD34+ progenitor cells to the injured microvasculature after acute myocardial infarction.

Keywords: Acute coronary syndrome; Microcirculation; Platelets; Progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / pathology*
  • Acute Coronary Syndrome / physiopathology
  • Aged
  • Angina, Stable / drug therapy
  • Angina, Stable / pathology*
  • Angina, Stable / physiopathology
  • Animals
  • Antigens, CD34 / metabolism
  • Blood Platelets / pathology*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Leukocytes, Mononuclear / pathology
  • Male
  • Mice
  • Microcirculation / physiology
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / physiopathology
  • Pilot Projects
  • Platelet Activation
  • Platelet Aggregation Inhibitors / therapeutic use
  • Risk Factors
  • Stem Cells / pathology*

Substances

  • Antigens, CD34
  • Extracellular Matrix Proteins
  • Platelet Aggregation Inhibitors