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Ca2+ Entry Through Reverse Mode Na+/Ca2+ Exchanger Contributes to Store Operated Channel-Mediated Neointima Formation After Arterial Injury. 2018

Bei Liu, and Bin Zhang, and Shiliang Huang, and Lixia Yang, and Carolyn M Roos, and Michael A Thompson, and Y S Prakash, and Jie Zang, and Jordan D Miller, and Ruiwei Guo
Department of Obstetrics and Gynecology, Kunming General Hospital, Kunming, Yunnan, China.

Na+/Ca2+ exchange (NCX) reversal-mediated Ca2+ entry is a critical pathway for stimulating proliferation in many cell lines. However, the role of reverse-mode NCX1 in neointima formation and atherosclerosis remains unclear. The aims of the present study were to investigate the functional role of NCX1 in the pathogenesis of atherosclerosis and vascular smooth muscle cell (VSMC) proliferation, and to determine the interaction between NCX1 and store depletion in VSMCs. A rat balloon injury model was established to examine the effect of the knockdown of NCX1 on neointima formation after injury. VSMCs were cultured to verify that NCX1 knockdown suppressed serum-induced VSMC proliferation. The results showed that balloon injury induced neointima formation and upregulated NCX1 expression at 7 and 14 days after injury in rat carotid arteries (1.18- and 1.45-fold, respectively). A lentivirus vector expressing short hairpin (sh)RNA against rat NCX1 dramatically downregulated NCX1, proliferating cell nuclear antigen (PCNA) and Ki-67 expression, and suppressed neointima formation in vivo (62% at 7 days and 70% at 14 days). KB-R7943 (an inhibitor of reverse-mode NCX1) and NCX1 knockdown significantly inhibited serum-induced VSMC proliferation (65% at 72 hours and 41% at 72 hours, respectively), determined according to PCNA and Ki-67 expression and cell counting in vitro, and markedly suppressed store depletion-mediated Ca2+ entry and peripheral cytosolic Na+ transients in VSMCs. Reverse-mode NCX1 is activated by store depletion and is required for proliferative VSMC proliferation and neointima formation after arterial injury.

UI MeSH Term Description Entries
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D002339 Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Arteries, Carotid,Artery, Carotid,Carotid Artery
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013890 Thiourea A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D050197 Atherosclerosis A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA. Atherogenesis,Atherogeneses,Atheroscleroses
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055785 Gene Knockdown Techniques The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES. Gene Knock Down Techniques,Gene Knock Down,Gene Knock-Down,Gene Knock-Down Techniques,Gene Knockdown,Gene Knock Downs,Gene Knock-Down Technique,Gene Knock-Downs,Gene Knockdown Technique,Gene Knockdowns,Knock Down, Gene,Knock Downs, Gene,Knock-Down Technique, Gene,Knock-Down Techniques, Gene,Knock-Down, Gene,Knock-Downs, Gene,Knockdown Technique, Gene,Knockdown Techniques, Gene,Knockdown, Gene,Knockdowns, Gene,Technique, Gene Knock-Down,Technique, Gene Knockdown,Techniques, Gene Knock-Down,Techniques, Gene Knockdown

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