SUMOylation as a Stress-Responsive Rheostat in Cardiovascular Disease
5 affiliations
- 1Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China
- 2Fisheries College, Ocean University of China, Qingdao 266003, China
- 3Haide College, Ocean University of China, Qingdao 266100, China
- 4Xuzhou Central Hospital, Southeast University, Xuzhou 221009, China
- 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
Abstract
SUMOylation is a reversible post-translational modification that regulates protein stability, localization, activity, and protein–protein interactions. In the cardiovascular system, SUMO signaling intersects with oxidative stress, mitochondrial homeostasis, calcium handling, inflammatory activation, and stress-induced transcriptional reprogramming. Here, we review the molecular architecture of the SUMO system and its redox sensitivity and integrate evidence for SUMO-dependent regulation of mitochondrial quality control, metabolic adaptation, inflammatory responses, and regulated cell death. We further examine how these mechanisms contribute to atherosclerosis, myocardial ischemia–reperfusion injury, cardiac remodeling, heart failure, arrhythmia, and pulmonary vascular disease, while distinguishing evidence that is mechanistic, correlative, or contradictory. Based on this evidence, we propose a stress-responsive SUMO rheostat framework in which the functional output of SUMO signaling is shaped not simply by the magnitude of stress, but by the interplay among stress intensity and duration, subcellular compartment, substrate accessibility and abundance, SUMO paralogue composition, enzyme activity, cell identity, and disease stage. These contextual variables can influence which SUMO-regulated substrates are accessible to individual enzymes, where modification occurs, and how long it persists, thereby contributing to divergent functional outcomes under otherwise similar stress conditions. The framework is intended as a conceptual synthesis for reconciling seemingly divergent effects of SUMOylation across cardiovascular diseases rather than as a quantitatively validated stress–SUMO response model. Finally, we discuss the translational challenges and opportunities of moving beyond global modulation of the SUMO pathway toward substrate-selective, enzyme-selective, and cell-targeted therapeutic strategies.
Related
- Dickkopf-3 (DKK3) in cardiovascular diseases: from a stress-responsive biomarker to a potential therapeutic target
- Integrated bulk and single-cell transcriptomic analyses with experimental validation identify PLOD1 as a diagnostic biomarker and TGF-β1-responsive profibrotic mediator in dupuytren’s disease
- DHX30 is a replication stress-responsive R-loop helicase that safeguards genome stability
- The Vagus Nerve–Macrophage Connection: Tuning the Rheostat of Regenerative Medicine
- Emerging extranuclear roles of protein SUMOylation in neuronal function and dysfunction
BibTeX
@article{su2026sumoylation,
title = {{SUMOylation as a Stress-Responsive Rheostat in Cardiovascular Disease}},
author = {Qiaoling Su and Yuejie Sun and Tongyao Zhuang and Qi Cheng and Wei Peng},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201838},
url = {https://www.mdpi.com/2073-4409/15/20/1838},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SUMOylation as a Stress-Responsive Rheostat in Cardiovascular Disease
AU - Qiaoling Su
AU - Yuejie Sun
AU - Tongyao Zhuang
AU - Qi Cheng
AU - Wei Peng
PY - 2026
DA - 2026/10/10
JO - Cells
DO - 10.3390/cells15201838
UR - https://www.mdpi.com/2073-4409/15/20/1838
AB - SUMOylation is a reversible post-translational modification that regulates protein stability, localization, activity, and protein–protein interactions. In the cardiovascular system, SUMO signaling intersects with oxidative stress, mitochondrial homeostasis, calcium handling, inflammatory activation, and stress-induced transcriptional reprogramming. Here, we review the molecular architecture of the SUMO system and its redox sensitivity and integrate evidence for SUMO-dependent regulation of mitochondrial quality control, metabolic adaptation, inflammatory responses, and regulated cell death. We further examine how these mechanisms contribute to atherosclerosis, myocardial ischemia–reperfusion injury, cardiac remodeling, heart failure, arrhythmia, and pulmonary vascular disease, while distinguishing evidence that is mechanistic, correlative, or contradictory. Based on this evidence, we propose a stress-responsive SUMO rheostat framework in which the functional output of SUMO signaling is shaped not simply by the magnitude of stress, but by the interplay among stress intensity and duration, subcellular compartment, substrate accessibility and abundance, SUMO paralogue composition, enzyme activity, cell identity, and disease stage. These contextual variables can influence which SUMO-regulated substrates are accessible to individual enzymes, where modification occurs, and how long it persists, thereby contributing to divergent functional outcomes under otherwise similar stress conditions. The framework is intended as a conceptual synthesis for reconciling seemingly divergent effects of SUMOylation across cardiovascular diseases rather than as a quantitatively validated stress–SUMO response model. Finally, we discuss the translational challenges and opportunities of moving beyond global modulation of the SUMO pathway toward substrate-selective, enzyme-selective, and cell-targeted therapeutic strategies.
SN - 2073-4409
ER -