Tags

Type your tag names separated by a space and hit enter

ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling.
Can J Cardiol. 2019 11; 35(11):1546-1556.CJ

Abstract

BACKGROUND

Endothelial progenitor cell (EPC) therapy has been suggested as a major breakthrough in the treatment of ischemic diseases. However, the molecular mechanism that underlies EPC functional regulation is still unclear.

METHODS

We examined the angiogenic capacity of EPCs in a hindlimb ischemia model of wild-type and ClC-3 knockout mice.

RESULTS

Mice lacking of ClC-3 exhibited reduced blood flow recovery and neovascularization in ischemic muscles 7 and 14 days after hind limb ischemia. Moreover, compared with wild-type EPCs, the hindlimb blood reperfusion in mice receiving ClC-3 knockout EPCs was significantly impaired, accompanied by reduced EPC homing and retention. In vitro, EPCs derived from ClC-3 knockout mice displayed impaired migratory, adhesive, and angiogenic activity. CXC chemokine receptor 4 (CXCR4) expression was significantly reduced in EPC from ClC-3 knockout mice compared with wild-type. Moreover, the expression and phosphorylation of Janus kinase 2 (JAK-2), a downstream signalling of CXCR4, was also reduced in ClC-3 knockout EPC, indicating that CXCR4/JAK-2 signalling is dysregulated by ClC-3 deficiency. Consistent with this assumption, the migratory capacity of wild-type EPCs was attenuated by either CXCR4 antagonist AMD3100 or JAK-2 inhibitor AG490. More importantly, the impaired migratory capacity of ClC-3 knockout EPCs was rescued by overexpression of CXCR4.

CONCLUSIONS

ClC-3 plays a critical role in the angiogenic capacity of EPCs and EPC-mediated neovascularization of ischemic tissues. Disturbance of CXCR4/JAK-2 signalling may contribute to the functional impairment of ClC-3 deficient EPCs. Thus, ClC-3 may be a potential therapeutic target for modulating neovascularization in ischemic diseases.

Authors+Show Affiliations

Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China. Electronic address: duyanhua@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31679624

Citation

Cheng, Li-Min, et al. "ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells By Decreasing CXCR4/JAK-2 Signalling." The Canadian Journal of Cardiology, vol. 35, no. 11, 2019, pp. 1546-1556.
Cheng LM, Li YJ, Chen XF, et al. ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling. Can J Cardiol. 2019;35(11):1546-1556.
Cheng, L. M., Li, Y. J., Chen, X. F., Li, X. L., Chen, X. S., & Du, Y. H. (2019). ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling. The Canadian Journal of Cardiology, 35(11), 1546-1556. https://doi.org/10.1016/j.cjca.2019.08.009
Cheng LM, et al. ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells By Decreasing CXCR4/JAK-2 Signalling. Can J Cardiol. 2019;35(11):1546-1556. PubMed PMID: 31679624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling. AU - Cheng,Li-Min, AU - Li,Yue-Jiao, AU - Chen,Xing-Feng, AU - Li,Xiao-Long, AU - Chen,Xiao-Shan, AU - Du,Yan-Hua, Y1 - 2019/08/17/ PY - 2019/02/28/received PY - 2019/08/03/revised PY - 2019/08/05/accepted PY - 2019/11/5/entrez PY - 2019/11/5/pubmed PY - 2020/5/14/medline SP - 1546 EP - 1556 JF - The Canadian journal of cardiology JO - Can J Cardiol VL - 35 IS - 11 N2 - BACKGROUND: Endothelial progenitor cell (EPC) therapy has been suggested as a major breakthrough in the treatment of ischemic diseases. However, the molecular mechanism that underlies EPC functional regulation is still unclear. METHODS: We examined the angiogenic capacity of EPCs in a hindlimb ischemia model of wild-type and ClC-3 knockout mice. RESULTS: Mice lacking of ClC-3 exhibited reduced blood flow recovery and neovascularization in ischemic muscles 7 and 14 days after hind limb ischemia. Moreover, compared with wild-type EPCs, the hindlimb blood reperfusion in mice receiving ClC-3 knockout EPCs was significantly impaired, accompanied by reduced EPC homing and retention. In vitro, EPCs derived from ClC-3 knockout mice displayed impaired migratory, adhesive, and angiogenic activity. CXC chemokine receptor 4 (CXCR4) expression was significantly reduced in EPC from ClC-3 knockout mice compared with wild-type. Moreover, the expression and phosphorylation of Janus kinase 2 (JAK-2), a downstream signalling of CXCR4, was also reduced in ClC-3 knockout EPC, indicating that CXCR4/JAK-2 signalling is dysregulated by ClC-3 deficiency. Consistent with this assumption, the migratory capacity of wild-type EPCs was attenuated by either CXCR4 antagonist AMD3100 or JAK-2 inhibitor AG490. More importantly, the impaired migratory capacity of ClC-3 knockout EPCs was rescued by overexpression of CXCR4. CONCLUSIONS: ClC-3 plays a critical role in the angiogenic capacity of EPCs and EPC-mediated neovascularization of ischemic tissues. Disturbance of CXCR4/JAK-2 signalling may contribute to the functional impairment of ClC-3 deficient EPCs. Thus, ClC-3 may be a potential therapeutic target for modulating neovascularization in ischemic diseases. SN - 1916-7075 UR - https://www.unboundmedicine.com/medline/citation/31679624/ClC_3_Deficiency_Impairs_the_Neovascularization_Capacity_of_Early_Endothelial_Progenitor_Cells_by_Decreasing_CXCR4/JAK_2_Signalling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0828-282X(19)31156-0 DB - PRIME DP - Unbound Medicine ER -