title: Hypoxic remodelling of Ca2+ stores does not alter human cardiac myofibroblast invasion.
abstract: Cardiac fibroblasts are the most abundant cell type in the heart, and play a key role in the maintenance and repair of the myocardium following damage such as myocardial infarction by transforming into a cardiac myofibroblast (CMF) phenotype. Repair occurs through controlled proliferation and migration, which are Ca(2+) dependent processes, and often requires the cells to operate within a hypoxic environment. Angiotensin converting enzyme (ACE) inhibitors reduce infarct size through the promotion of bradykinin (BK) stability. Although CMF express BK receptors, their activity under the reduced O(2) conditions that occur following infarct are entirely unexplored. Using Fura-2 microfluorimetry on primary human CMF, we found that hypoxia significantly increased the mobilisation of Ca(2+) from intracellular stores in response to BK whilst capacitative Ca(2+) entry (CCE) remained unchanged. The enhanced store mobilisation was due to a striking increase in CMF intracellular Ca(2+)-store content under hypoxic conditions. However, BK-induced CMF migration or proliferation was not affected following hypoxic exposure, suggesting that Ca(2+) influx rather than mobilisation is of primary importance in CMF migration and proliferation.
authors.affiliation: Leeds Institute for Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: K
authors.initials: K
authors.lastname: Riches
authors.forename: N T
authors.initials: NT
authors.lastname: Hettiarachchi
authors.forename: K E
authors.initials: KE
authors.lastname: Porter
authors.forename: C
authors.initials: C
authors.lastname: Peers
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018002:Receptors, Bradykinin / Q000378:metabolism
chemical_list: D018002:Receptors, Bradykinin; D002118:Calcium