title: Calcium-sensing receptor-mediated mitogen-activated protein kinase pathway improves the status of transplanted mouse embryonic stem cells in rats with acute myocardial infarction.
abstract: Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity. These findings indicate that cardiac function could be enhanced significantly by combination therapy with CaSR inhibition and ESC transplantation; the effect was better than ESC transplantation alone, and the mechanism might be associated with a reduction in cell apoptosis via the inhibition of the MAPK pathway. Apoptosis could be reduced through CaSR, which regulates the MAPK pathway and apoptosis-related protein. Our study indicated that CaSR inhibitors have a pivotal role in the treatment of AMI.
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China. mdjsunjian@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Bai
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Yu
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Gaochen
authors.initials: G
authors.lastname: Song
authors.affiliation: Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Luan
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D002460:Cell Line; D005786:Gene Expression Regulation; D064593:Heterografts; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D033581:Stem Cell Transplantation
chemical_list: D051017:Apoptosis Regulatory Proteins; C577923:CASR protein, mouse; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; C473605:extracellular calcium cation-sensing receptor, rat
keywords: Acute myocardial infarction; Calcium-sensing receptor; Cardiac function; Cellular transplant; Embryonic stem cells