New insights into lipid raft function regulating myocardial vascularization competency in human idiopathic dilated cardiomyopathy

Santiago Roura, Carolina Gálvez-Montón, Josep M. Pujal, Laura Casani, Marco A. Fernández, Laura Astier, Paloma Gastelurrutia, Maite Domingo, Cristina Prat-Vidal, Carolina Soler-Botija, Aida Llucià-Valldeperas, Vicenta Llorente-Cortés, Antoni Bayes-Genis

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Objective: Idiopathic dilated cardiomyopathy (IDCM) affects myocardial vascularization. Whether a lack of demand for increased myocardial vascularization and/or an impaired response of circulating angiogenic-supportive cells are responsible for the vascular derangements found in IDCM is unknown. Methods and results: Left ventricle (LV) samples obtained at transplant from IDCM hearts were compared to control hearts from non-cardiac decedents. Peripheral colony-forming myeloid cells were extracted from age- and sex-matched IDCM patients and healthy volunteers. At the tissue level, no differences were detected in stromal cell-derived factor (SDF)-1α expression, but integrin-linked kinase (ILK) levels and activity were increased in IDCM. A marked co-localization of SDF-1α and the specific marker of cholesterol-enriched lipid rafts Flotillin (Flot)-1 was found in IDCM. SDF-1α was also highly distributed into IDCM lipid rafts. Non-adherent pro-angiogenic cells from both groups, which were found increased in patients but showed similar surface levels of CXCR-4, equally supported Matrigel-mediated cell network formation. However, SDF-1-mediated migration was reduced in IDCM-derived cells, which also exhibited decreased ILK activity and downstream ERK activation. Conclusions: Taken together, our results point out that myocardial competency to increase vascularization is not altered in IDCM, but dysfunctional SDF-1-mediated migration by peripheral pro-angiogenic cells through ILK and downstream ERK signaling may compromise endothelial recovery in patients. We provide new insights into lipid raft function in human IDCM and envision more effective treatments. © 2013 Elsevier Ireland Ltd.
Original languageEnglish
Pages (from-to)354-364
JournalAtherosclerosis
Volume230
Issue number2
DOIs
Publication statusPublished - 1 Oct 2013

Keywords

  • Angiogenic-supportive myeloid cells
  • Idiopathic dilated cardiomyopathy
  • ILK
  • Lipid rafts
  • SDF-1

Fingerprint Dive into the research topics of 'New insights into lipid raft function regulating myocardial vascularization competency in human idiopathic dilated cardiomyopathy'. Together they form a unique fingerprint.

Cite this