title: Loss of CEACAM1, a Tumor-Associated Factor, Attenuates Post-infarction Cardiac Remodeling by Inhibiting Apoptosis.
abstract: Carcinoembryonic antigen-related cell adhesion molecule1 (CEACAM1) is a tumor-associated factor that is known to be involved in apoptosis, but the role of CEACAM1 in cardiovascular disease is unclear. We aims to investigate whether CEACAM1 influences cardiac remodeling in mice with myocardial infarction (MI) and hypoxia-induced cardiomyocyte injury. Both serum in patients and myocardial CEACAM1 levels in mice were significantly increased in response to MI, while levels were elevated in neonatal rat cardiomyocytes (NRCs) exposed to hypoxia. Eight weeks after MI, a lower mortality rate, improved cardiac function, and less cardiac remodeling in CEACAM1 knock-out (KO) mice than in their wild-type (WT) littermates were observed. Moreover, myocardial expression of mitochondrial Bax, cytosolic cytochrome C, and cleaved caspase-3 was significantly lower in CEACAM1 KO mice than in WT mice. In cultured NRCs exposed to hypoxia, recombinant human CEACAM1 (rhCEACAM1) reduced mitochondrial membrane potential, upregulated mitochondrial Bax, increased cytosolic cytochrome C and cleaved caspase-3, and consequently increased apoptosis. RhCEACAM1 also increased the levels of GRP78 and CHOP in NRCs with hypoxia. All of these effects were abolished by silencing CEACAM1. Our study indicates that CEACAM1 exacerbates hypoxic cardiomyocyte injury and post-infarction cardiac remodeling by enhancing cardiomyocyte mitochondrial dysfunction and endoplasmic reticulum stress-induced apoptosis.
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Nvqin
authors.initials: N
authors.lastname: He
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.|Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, 450003, China.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Gangbin
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004452:Echocardiography; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D020257:Ventricular Remodeling; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D051742:Transcription Factor CHOP; D045304:Cytochromes c; D053148:Caspase 3