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Updated: Jul 27, 2025

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
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Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

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SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling

Yue Xu1,2, Haifeng Zhang1,2, Jordan S Pober1,2

  • 1Interdepartmental Program in Vascular Biology and Therapeutics, Department of Pathology, Yale University School of Medicine, New Haven, CT.

Research Square
|June 9, 2023
PubMed

Insights

Senp1 deficiency in vascular smooth muscle cells increases SUMOylated serum response factor (SRF), promoting cardiovascular disease. Targeting the SRF-ELK complex offers potential therapeutic strategies for cardiovascular diseases.

Area of Science:

  • Molecular biology
  • Cardiovascular research
  • Cellular signaling

Background:

  • Serum response factor (SRF) regulates vascular smooth muscle cell (VSMC) phenotype, crucial in cardiovascular diseases (CVD).
  • Post-translational modification, specifically SUMOylation, is implicated in SRF regulation, but its role in CVD remains unclear.

Approach:

  • Investigated the impact of Senp1 deficiency on SRF SUMOylation and its consequences in VSMCs.
  • Utilized mouse models and patient-derived cells to elucidate the mechanism of SRF SUMOylation in vascular remodeling.
  • Examined the effect of targeting the SRF-ELK complex using AZD6244 in Senp1-deficient mice.

Key Points:

  • Senp1 deficiency in VSMCs enhances SRF SUMOylation at lysine 143, increasing nuclear accumulation and promoting a shift from myocardin to phosphorylated ELK1 cofactors.
  • This SRF-ELK complex formation drives VSMC proliferation, migration, and synthetic phenotype, exacerbating vascular remodeling and neointimal hyperplasia.
  • Elevated SUMOylated SRF and phosphor-ELK1 were observed in VSMCs from CVD patients' coronary arteries.

Conclusions:

  • Senp1-mediated regulation of SRF SUMOylation is critical for maintaining VSMC homeostasis and preventing pathological vascular remodeling.
  • The SRF-ELK complex is a key driver of CVD pathogenesis, representing a potential therapeutic target.
  • Targeting the SRF complex, specifically the SRF-ELK interaction, may offer a novel strategy for treating cardiovascular diseases.
Keywords:
ELK1SRFSUMOylationVascular remodelingneointimasmooth muscle cell

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