Cardioprotective Effect of the SDF-1α/CXCR4 Axis in Ischemic Postconditioning in Isolated Rat Hearts.
- Author:
Jeong Su KIM
1
;
Youngho JANG
;
June Hong KIM
;
Yong Hyun PARK
;
Sun Ae HWANG
;
Jun KIM
;
Sung Ryul LEE
;
Zhelong XU
;
Changill BAN
;
Kyohan AHN
;
Kook Jin CHUN
Author Information
- Publication Type:Original Article
- Keywords: Reperfusion injury; Ischemic postconditioning; Stromal cell-derived factor-1α; CXCR4 receptors
- MeSH: Animals; Creatine Kinase; Electrocardiography; Family Characteristics; Heart*; Hemodynamics; Ischemia; Ischemic Postconditioning*; L-Lactate Dehydrogenase; Phosphorylation; Phosphotransferases; Rats*; Receptors, CXCR4; Reperfusion; Reperfusion Injury
- From:Korean Circulation Journal 2017;47(6):949-959
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: Information about the role of the stromal cell-derived factor-1α (SDF-1α)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the SDF-1α/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC. METHODS: Isolated rat hearts were divided into four groups. The control group was subjected to 30-min of regional ischemia and 2-hour of reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4 antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC group, n=11) and control group (AMD group, n=9). Hemodynamic changes with electrocardiography were monitored and infarct size was measured. The SDF-1α, lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate were measured. We also analyzed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation state expression. RESULTS: IPOC significantly reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC. IPOC significantly decreased LDH and CK, but these effects were reversed by AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects were blocked by AMD3100. CONCLUSION: Based on the results of this study, SDF-1α/CXCR4 signaling may be involved in IPOC cardioprotection and this signaling pathway couples to the ERK1/2 and Akt pathways.
