Paracrine effects of hypoxic fibroblast-derived factors on the MPT-ROS threshold and viability of adult rat cardiac myocytes

摘要

Hypoxia is a major factor influencing the extent of cell injury and response in myocardial ischemia and infarction. The response of different cell types to hypoxia depends on intrinsic adaptive mechanisms. In cardiomyocytes, hypoxia triggers mitochondrial permeability transition (MPT) and apoptosis (20, 27). Cardiac fibroblasts, on the other hand, are resistant to hypoxic injury (22), and it has been reported that hypoxia reduces DNA synthesis in these cells (1). Moreover, recent studies in our laboratory show that hypoxia causes reversible cell cycle arrest in cardiac fibroblasts (unpublished observations), which might help conserve energy stores and, possibly, prevent cell death. The present study examined whether factors released from cardiac fibroblasts in response to hypoxia may modify these diverse cellular responses to the primary stimulus.