Calcium promotes vascular smooth muscle cell phenotypic switching in Marfan syndrome

被引：2

作者：

Yang, Yunxiao ^{[1
]}

Xie, Enzehua ^{[2
]}

Liu, Yuhua ^{[1
]}

Peng, Zhan ^{[1
]}

Yu, Cuntao ^{[2
]}

Hua, Kun ^{[1
]}

Yang, Xiubin ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiovasc Surg, Beijing 100029, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Dept Cardiovasc Surg, Beijing 100047, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2023年 / 665卷

关键词：

Marfan syndrome; Vascular smooth muscle cell; Phenotypic switching; Calcium; AORTIC-ANEURYSM; PROLIFERATION; SERCA;

D O I：

10.1016/j.bbrc.2023.05.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fibrillin 1 (Fbn1) mutations cause Marfan syndrome (MFS), with aortic root dilatation, dissection, and rupture. Few studies reported the blood calcium and lipid profile of MFS, and the effect of vascular smooth muscle cell (VSMC) phenotypic switching on MFS aortic aneurysm is unclear. Here, we aimed to investigate the role of calcium-related VSMC phenotypic switching in MFS. We retrospectively collected MFS patients' clinical data, performed bioinformatics analysis to screen the enriched biological process in MFS patients and mice, and detected markers of VSMC phenotypic switching on Fbn1C1039G/ thorn mice and primary aortic vascular smooth muscle cells. We found that patients with MFS have elevated blood calcium levels and dyslipidemia. Furthermore, the calcium concentration levels were increased with age in MFS mice, accompanied by the promoted VSMC phenotypic switching, and SERCA2 contributed to maintaining the contractile phenotype of VSMCs. This study provides the first evidence that the increased calcium is associated with the promoted VSMC phenotype switching in MFS. SERCA may become a novel therapeutic target for suppressing aneurysm progression in MFS. (c) 2023 Elsevier Inc. All rights reserved.

引用

页码：124 / 132

页数：9

共 36 条

[1] Triglyceride Metabolism in the Liver [J].

Alves-Bezerra, Michele ;

Cohen, David E. .

COMPREHENSIVE PHYSIOLOGY, 2018, 8 (01) :1-22

[2] Inhibition of HIPK2 Alleviates Thoracic Aortic Disease in Mice With Progressively Severe Marfan Syndrome [J].

Caescu, Cristina, I ;

Hansen, Jens ;

Crockett, Brittany ;

Xiao, Wenzhen ;

Arnaud, Pauline ;

Spronck, Bart ;

Weinberg, Alan ;

Hashimoto, Takeshi ;

Murtada, Sae-Il ;

Borkar, Roshan ;

Gallo, James M. ;

Jondeau, Guillaume ;

Boileau, Catherine ;

Humphrey, Jay D. ;

He, John Cijiang ;

Iyengar, Ravi ;

Ramirez, Francesco .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2021, 41 (09) :2483-2493

[3] Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation [J].

Choi, Seung Hee ;

Park, Sungmi ;

Oh, Chang Joo ;

Leem, Jaechan ;

Park, Keun-Gyu ;

Lee, In-Kyu .

VASCULAR PHARMACOLOGY, 2015, 73 :11-19

[4] Dimorphic Effects of Transforming Growth Factor-β Signaling During Aortic Aneurysm Progression in Mice Suggest a Combinatorial Therapy for Marfan Syndrome [J].

Cook, Jason R. ;

Clayton, Nicholas P. ;

Carta, Luca ;

Galatioto, Josephine ;

Chiu, Emily ;

Smaldone, Silvia ;

Nelson, Carol A. ;

Cheng, Seng H. ;

Wentworth, Bruce M. ;

Ramirez, Francesco .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2015, 35 (04) :911-U195

[5] A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome [J].

Doyle, Jefferson J. ;

Doyle, Alexander J. ;

Wilson, Nicole K. ;

Habashi, Jennifer P. ;

Bedja, Djahida ;

Whitworth, Ryan E. ;

Lindsay, Mark E. ;

Schoenhoff, Florian ;

Myers, Loretha ;

Huso, Nick ;

Bachir, Suha ;

Squires, Oliver ;

Rusholme, Benjamin ;

Ehsan, Hamid ;

Huso, David ;

Thomas, Craig J. ;

Caulfield, Mark J. ;

Van Eyk, Jennifer E. ;

Judge, Daniel P. ;

Dietz, Harry C. .

ELIFE, 2015, 4

[6] 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases (vol 35, pg 2873, 2014) [J].

Erbel, R. ;

Aboyans, V. ;

Boileau, C. ;

Bossone, E. ;

Di Bartolomeo, R. ;

Eggebrecht, H. ;

Evangelista, A. ;

Falk, V. ;

Frank, H. ;

Gaemperli, O. ;

Grabenwoger, M. ;

Haverich, A. ;

Iung, B. ;

Manolis, A. John ;

Meijboom, F. ;

Nienaber, C. A. ;

Roffi, Marco ;

Rousseau, H. ;

Sechtem, U. ;

Sirnes, Per A. ;

Von Allmen, R. S. ;

Vrints, C. J. M. .

EUROPEAN HEART JOURNAL, 2015, 36 (41) :2779-2779

[7] MARFAN-SYNDROME - LONG-TERM SURVIVAL AND COMPLICATIONS AFTER AORTIC-ANEURYSM REPAIR [J].

FINKBOHNER, R ;

JOHNSTON, D ;

CRAWFORD, ES ;

COSELLI, J ;

MILEWICZ, DM .

CIRCULATION, 1995, 91 (03) :728-733

[8] Preparation of primary cultured mesenteric artery smooth muscle cells for fluorescent imaging and physiological studies [J].

Golovina, Vera A. ;

Blaustein, Mordecai P. .

NATURE PROTOCOLS, 2006, 1 (06) :2681-2687

[9] Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm A Meta-analysis [J].

Harrison, Seamus C. ;

Holmes, Michael V. ;

Burgess, Stephen ;

Asselbergs, Folkert W. ;

Jones, Gregory T. ;

Baas, Annette F. ;

van 't Hof, F. N. ;

de Bakker, Paul I. W. ;

Blankensteijn, Jan D. ;

Powell, Janet T. ;

Saratzis, Athanasios ;

de Borst, Gert J. ;

Swerdlow, Daniel I. ;

van der Graaf, Yolanda ;

van Rij, Andre M. ;

Carey, David J. ;

Elmore, James R. ;

Tromp, Gerard ;

Kuivaniemi, Helena ;

Sayers, Robert D. ;

Samani, Nilesh J. ;

Bown, Matthew J. ;

Humphries, Steve E. .

JAMA CARDIOLOGY, 2018, 3 (01) :26-33

[10] Role of Cholesterol-Associated Steatohepatitis in the Development of NASH [J].

Horn, Christian L. ;

Morales, Amilcar L. ;

Savard, Christopher ;

Farrell, Geoffrey C. ;

Ioannou, George N. .

HEPATOLOGY COMMUNICATIONS, 2022, 6 (01) :12-35

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