Empagliflozin Alleviates Atherosclerotic Calcification by Inhibiting Osteogenic Differentiation of Vascular Smooth Muscle Cells
Junping LiChangping LiZhaoqi HuangChunling HuangJuanzhang LiuTao WuShuwan XuPeibiao MaiDeng-feng GengShuxian ZhouKun ZhangZhaoyu Liu
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Objective: SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. The aim of this study is to determine if repurposing empagliflozin is beneficial in the treatment of atherosclerotic calcification.Methods: ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Body weight was weekly monitored. After 24 weeks feeding, serum lipid levels, fasting and ad libitum blood glucose levels were measured. Arterial calcification was assessed by alizarin red and von kossa staining in aortic roots. Calcification of vascular smooth muscle cells (VSMCs) and aortic rings were induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin was further performed to analyze the underlying mechanisms. qRT-PCR was used to detect the marker gene expression of osteogenic differentiation of VSMCs. Results: Empagliflozin treatment significantly alleviated arterial calcification during atherosclerosis in ApoE-/- mice, while had little effect on body weight and blood glucose levels. Also, empagliflozin significantly inhibits calcification of primary VSMCs and aortic rings in vitro. Additionally, empagliflozin significantly inhibits osteogenic differentiation of VSMCs.Conclusion: Empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.Keywords:
Empagliflozin
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In this review, the aim is to discuss the pathological development of vascular calcification including a brief description of arterial wall structure and function, the development of atherosclerosis, highlighting normal physiological and vascular calcification with particular emphasis on their common characteristics, critically review the recent findings implicating the role of vascular smooth muscle cells in the pathogenesis of the calcification process including the role of microRNAs in regulation of these cells phenotype as a target to control cardiovascular calcification.
Pathogenesis
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Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)
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The accumulation of calcium in atherosclerotic plaques is a prominent feature of advanced atherosclerosis, and it has a strong positive correlation with the total burden of atherosclerosis. Atherosclerotic calcification usually appears first at the necrotic core, indicating that cell death and inflammatory processes are involved in calcification. During atherosclerotic inflammation, various cell types, such as vascular smooth muscle cells, nascent resident pericytes, circulating stem cells, or adventitial cells, have been assumed to differentiate into osteoblastic cells, which lead to vascular calcification. Among these cell types, vascular smooth muscle cells are considered a major contributor to osteochondrogenic cells in the atherosclerotic milieu. In this review, we summarize the molecular mechanisms underlying the osteochondrogenic switch of vascular smooth muscle cells in atherosclerotic plaques.
Cell type
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Senescence
Cellular senescence
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Бұл зерттеужұмысындaКaно моделітурaлы жәнеоғaн қaтыстытолықмәліметберілгенжәнеуниверситетстуденттерінебaғыттaлғaн қолдaнбaлы (кейстік)зерттеужүргізілген.АхметЯссaуи университетініңстуденттеріүшін Кaно моделіқолдaнылғaн, олaрдың жоғaры білімберусaпaсынa қоятынмaңыздытaлaптaры, яғнисaпaлық қaжеттіліктері,олaрдың мaңыздылығытурaлы жәнесaпaлық қaжеттіліктерінеқaтыстыөз университетінқaлaй бaғaлaйтындығытурaлы сұрaқтaр қойылғaн. Осы зерттеудіңмaқсaты АхметЯсaуи университетіндетуризмменеджментіжәнеқaржы бaкaлaвриaт бaғдaрлaмaлaрыныңсaпaсынa қaтыстыстуденттердіңқaжеттіліктерінaнықтaу, студенттердіңқaнaғaттaну, қaнaғaттaнбaу дәрежелерінбелгілеу,білімберусaпaсын aнықтaу мен жетілдіружолдaрын тaлдaу болыптaбылaды. Осы мaқсaтқaжетуүшін, ең aлдыменКaно сaуaлнaмaсы түзіліп,116 студенткеқолдaнылдыжәнебілімберугежәнеоның сaпaсынa қaтыстыстуденттердіңтaлaптaры мен қaжеттіліктерітоптықжұмыстaрaрқылыaнықтaлды. Екіншіден,бұл aнықтaлғaн тaлaптaр мен қaжеттіліктерКaно бaғaлaу кестесіменжіктелді.Осылaйшa, сaпa тaлaптaры төрт сaнaтқa бөлінді:болуытиіс, бір өлшемді,тaртымдыжәнебейтaрaп.Соңындa,қaнaғaттaну мен қaнaғaттaнбaудың мәндеріесептелдіжәнестуденттердіңқaнaғaттaну мен қaнaғaттaнбaу деңгейлерінжоғaрылaту мен төмендетудеосытaлaптaр мен қaжеттіліктердіңрөліaйқын aнықтaлды.Түйінсөздер:сaпa, сaпaлық қaжеттіліктер,білімберусaпaсы, Кaно моделі.
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The nationally-recognized Susquehanna
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singing that will take you to new
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Vascular smooth muscle cells play a pivotal role in the pathogenesis of medial
calcification. We have recently demonstrated expression of the calcium sensing receptor
(CaSR) in human aortic smooth muscle cells (HAoSMC) and human arteries and
demonstrated a correlation between CaSR expression and medial calcification. Here we have
examined downstream CaSR-mediated signaling pathways in HAoSMC and investigated the
role of the CaSR in regulating HAoSMC proliferation and apoptosis.
Pathogenesis
Calcium Signaling
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