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Updated: Jan 12, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
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Published on: May 31, 2016

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Focal Adhesion Kinase Promotes Calcification of Vascular Smooth Muscle Cells via Regulation of Histone Deacetylase 4

Wenjie Tian1,2,3, Kuldeep Singh1, Lova P Kajuluri1

  • 1Cardiovascular Research Center and Cardiology Division of the Heart and Vascular Institute, Boston (W.T., K.S., L.P.K., S.L., K.R., C.J.N., W.J., H.J.B., S.B., K.O., R.H.L., C.B., E.M., H.T., H.H.S., M.S.M., A.L.J., E.L.C., M.E.L., C.L.L.C., R.M.).

Arteriosclerosis, Thrombosis, and Vascular Biology
|October 30, 2025
PubMed
Abstract

Insights

Focal adhesion kinase (FAK) promotes vascular calcification by regulating histone deacetylases (HDACs) 4 and 5. Targeting FAK, HDAC4, and HDAC5 may offer new treatments for vascular calcification.

Area of Science:

  • Vascular Biology
  • Cell Biology
  • Molecular Medicine

Background:

  • Vascular calcification is an active process involving the osteogenic transition of vascular smooth muscle cells (VSMCs).
  • Focal adhesion kinase (FAK) influences bone formation by regulating histone deacetylase (HDAC) 4 and 5 localization.
  • The role of FAK in vascular calcification via HDAC regulation in VSMCs remains unclear.

Purpose of the Study:

  • To investigate the role of FAK in VSMC calcification.
  • To determine if FAK regulates vascular calcification through HDAC4 and HDAC5.
  • To explore FAK as a potential therapeutic target for vascular calcification.

Main Methods:

  • Utilized perturbational assays, including pharmacological inhibition and gene silencing of FAK.
  • Assessed effects on VSMC calcification, migration, and procalcification factor expression.
  • Examined the impact of inhibiting HDAC nuclear export and analyzed FAK expression in human coronary arteries.

Main Results:

  • HDAC4 and HDAC5 are identified as positive regulators of vascular calcification.
  • FAK inhibition blocked VSMC calcification, reduced procalcification factors, and decreased cell migration.
  • FAK inhibition enhanced nuclear localization of HDAC4 and HDAC5, and attenuated arterial calcification ex vivo.

Conclusions:

  • FAK promotes VSMC calcification, partly through HDAC4 and HDAC5 phosphorylation.
  • Targeting FAK, HDAC4, and HDAC5 presents a potential therapeutic strategy for vascular calcification.
Keywords:
focal adhesion protein-tyrosine kinaseshistone deacetylasesmuscle, smooth, vascularphenotypevascular calcification

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