Related Experiment Video

Updated: Apr 5, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

20.7K

SERCA2 dysfunction drives vascular calcification via coupling with TSPO-MCU at mitochondria-associated endoplasmic

Shixian Pi1, Wanling Liu2, Junyong Zhao2

  • 1Department of Cardiology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China; Department of Cardiology, People's Liberation Army Joint Logistic Support Force 945th Hospital, Yaan 625000, China.

Pharmacological Research
|April 3, 2026
PubMed

Insights

Vascular smooth muscle cell (VSMC) calcification is worsened by SERCA2 dysfunction, which increases mitochondrial calcium overload via TSPO-dependent MAM formation. Targeting TSPO may treat vascular calcification.

Area of Science:

  • Cardiovascular Biology
  • Cellular Metabolism
  • Molecular Medicine

Background:

  • Vascular calcification involves vascular smooth muscle cell (VSMC) osteogenic transdifferentiation driven by calcium signaling.
  • Sarcoplasmic/ER calcium ATPase 2 (SERCA2) regulates intracellular calcium; its dysfunction, marked by Cys674 oxidation, is implicated but poorly understood in vascular calcification.

Purpose of the Study:

  • To investigate the role of SERCA2 dysfunction in vascular calcification.
  • To elucidate the underlying molecular mechanisms involving mitochondria-associated endoplasmic reticulum membranes (MAM) and translocator protein (TSPO).

Main Methods:

  • Utilized heterozygous SERCA2 Cys674Ser knock-in (SKI) mice and cultured VSMC.
  • Analyzed aortic calcification in response to vitamin D3 overload and chronic kidney disease (CKD) models.
  • Investigated the role of TSPO and the IP3R1-Grp75-VDAC1-MCU complex in MAM formation and calcium handling.

Main Results:

  • Oxidized SERCA2 C674 was elevated in calcified arteries of mice and CKD patients.
  • SERCA2 dysfunction exacerbated aortic calcification, mitochondrial impairment, and calcium overload in VSMC.
  • TSPO knockdown alleviated, while overexpression aggravated, SERCA2 dysfunction-induced MAM formation and vascular calcification.

Conclusions:

  • SERCA2 dysfunction promotes TSPO-dependent MAM formation, linking SERCA2 to the IP3R1-Grp75-VDAC1-MCU complex.
  • This coupling leads to mitochondrial impairment and calcium overload, driving vascular calcification.
  • The study identifies SERCA2 and TSPO as key players and potential therapeutic targets for vascular calcification.
Keywords:
Mitochondria-associated endoplasmic reticulum membranesMitochondrial calcium uniporterSERCA2Translocator proteinVascular calcification

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