Effect of hypoxic paracrine media on calcium-regulatory proteins in infarcted rat myocardium.
OBJECTIVE
An increase in intracellular calcium concentration due to loss of Ca(2+) homeostasis triggers arrhythmia or cardiac cell death in the heart. Paracrine factors released from stem cells have beneficial cardioprotective effects. However, the mechanism of modulation of Ca(2+) homeostasis by paracrine factors in ischemic myocardium remains unclear.


METHODS
We isolated rat bone marrow-derived mesenchymal stem cells (MSCs), and prepared paracrine media (PM) from MSCs under hypoxic or normoxic conditions (hypoxic PM and normoxic PM). We induced rat myocardial infarction by left anterior descending ligation for 1 hour, and treated PM into the border region of infarcted myocardium (n=6/group) to identify the alteration in calcium-regulated proteins. We isolated and stained the heart tissue with specific calcium-related antibodies after 11 days.


RESULTS
The hypoxic PM treatment increased Ca(2+)-related proteins such as L-type Ca(2+) channel, sarcoplasmic reticulum Ca(2+) ATPase, Na(+)/K(+) ATPase, and calmodulin, whereas the normoxic PM treatment increased those proteins only slightly. The sodium-calcium exchanger was significantly reduced by hypoxic PM treatment, compared to moderate suppression by the normoxic PM treatment.


CONCLUSIONS
Our results suggest that hypoxic PM was significantly associated with the positive regulation of Ca(2+) homeostasis in infarcted myocardium.
Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea.
Byeong-Wook
BW
Song
Division of Cardiology, Severance Cardiovascular Research Center, Yonsei University College of Medicine, Seoul, Korea.
Hye Jin
HJ
Hwang
Division of Cardiology, Severance Cardiovascular Research Center, Yonsei University College of Medicine, Seoul, Korea.
Minji
M
Seung
Division of Cardiology, Severance Cardiovascular Research Center, Yonsei University College of Medicine, Seoul, Korea.
Moon-Hyoung
MH
Lee
Calcium homeostasis endoplasmic reticulum protein; Myocardial infarction; Paracrine communication; Stem cells