Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
Vascular Biology and Vascular Medicine
Heparin Induces the Mobilization of Heart-Derived Multipotent Mesoangioblasts During Cardiac Surgery With Cardiopulmonary Bypass or Cardiac Catheterization
Yoshihiro HataMasayoshi IwasakiKeisuke FujitakaHaengnam ParkDaisuke SatoChiharu EnokiNaoki MinatoKeita HoritaniMiyuki NakanoHiroshi KishimotoKensaku WadaMasamichi KoyanagiYasushi AdachiYoshihiro YamamotoAndreas M. ZeiherStefanie DimmelerIchiro Shiojima
Author information

2018 Volume 82 Issue 5 Pages 1459-1465


Background:We previously identified circulating mesoangioblasts (cMABs), a subset of mesenchymal stem cells that express cardiac mesodermal markers, in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). We also found that hepatocyte growth factor (HGF) is upregulated during cardiac surgery with CPB in humans, and induces MAB-like cell mobilization in rodents. These results strongly suggest that heparin induced MAB mobilization via HGF upregulation. Here, we tested this hypothesis in patients undergoing cardiac surgery or cardiac catheterization. We also examined whether human cMABs are derived from the heart.

Methods and Results:Plasma HGF levels were determined by ELISA. Mononuclear cells isolated from blood samples were cultured on fibronectin-coated dishes, and outgrowing cMAB colonies were counted. We first confirmed that HGF upregulation and cMAB mobilization were observed before the start of CPB, excluding the possibility that CPB is the primary inducer of cMAB mobilization. We then examined patients undergoing cardiac catheterization and found that heparin significantly increased plasma HGF levels and the number of cMAB colonies in a dose-dependent manner. The results of simultaneous blood sampling from the aortic sinus, coronary sinus, and right atrium were consistent with the notion that human cMABs are derived from the heart.

Conclusions:Human cMABs are mobilized by heparin injection during cardiac surgery or cardiac catheterization, presumably via HGF upregulation.

Information related to the author
Previous article Next article