The homing of bone marrow stem cells is differentially activated in ischemic and valvular heart diseases and influenced by beta-blockers

J Transl Med. 2018 May 21;16(1):133. doi: 10.1186/s12967-018-1520-9.

Abstract

Background: Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases.

Methods: The SDF-1 and inflammatory profile were analyzed by ELISA from plasma obtained bone marrow of ischemic heart patients (IHD, n = 41), valvular heart patients (VHD, n = 30) and healthy controls (C, n = 9). Flow cytometry was used to evaluate CXCR4 (CD184) expression on the surface of bone marrow cells, and the CXCR4 expression was estimated by real-time quantitative PCR.

Results: The SDF-1 levels in the groups IHD, VHD and control were, respectively, 230, 530 and 620 pg/mL (P = 0.483), and was decreased in VHD patients using beta-blockers (263 pg/mL) when compared with other (844 pg/mL) (P = 0.023). Compared with IHD, the VHD group showed higher CXCR4 (P = 0.071) and CXCR7 (P = 0.082) mRNA expression although no difference in the level of CXCR4+ bone marrow cells was found between groups (P = 0.360).

Conclusion: In conclusion, pathophysiological differences between IHD and VHD can affect the molecules involved in the activation of homing. In addition, the use of beta-blockers appears to interfere in this mechanism, a fact that should be considered in protocols that use BMC.

Keywords: CXCR4; CXCR7; Cell homing; Ischemic heart disease; Stromal cell-derived factor-1; Valvular heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism
  • Chemokine CXCL12 / metabolism
  • Female
  • Heart Valve Diseases / genetics
  • Heart Valve Diseases / pathology
  • Heart Valve Diseases / therapy*
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / therapy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • ACKR3 protein, human
  • Adrenergic beta-Antagonists
  • Biomarkers
  • Chemokine CXCL12
  • Inflammation Mediators
  • RNA, Messenger
  • Receptors, CXCR
  • Receptors, CXCR4
  • Tumor Necrosis Factor-alpha