Activated Protein C Suppresses Cardiomyocyte Senescence in Diabetic Cardiomyopathy via PAR1/PAR3-P85-CaMKIIδ Axis
Diabetes exacerbates cardiomyocyte senescence, leading to an accelerated decline in cardiac function. The systemic levels of activated protein C (aPC) were reduced, which correlated with deterioration of cardiac diastolic function in diabetic cardiomyopathy (DbCM), while the underlying mechanisms remained unclear. We aim to identify the role of aPC in ameliorating cardiomyocyte senescence in DbCM. We highlighted that aPC ameliorated cardiomyocyte senescence in DbCM via the PAR1/PAR3-P85-CaMKIIδ axis with genetic (TMP/P) and interventional (PC injection) diabetic mouse models. These findings could lead to increased insight into the pathogenesis and innovative therapeutic approaches of diabetic cardiomyopathy.
Authors
- Hesong Zeng (ORCID: https://orcid.org/0000-0001-5160-4427)
- Tamás Atlasz (ORCID: https://orcid.org/0000-0002-8112-8633)
- Lingyun Luo
- Thati Madhusudhan (ORCID: https://orcid.org/0000-0003-0631-8725)
- Alexandra Váczy
- Xiaodan Zhong (ORCID: https://orcid.org/0000-0001-5268-3905)
- Mengwen Wang
- L. Wang (ORCID: https://orcid.org/0009-0005-4857-5422)
- Hongjie Wang (ORCID: https://orcid.org/0000-0002-0169-4257)
- Yueqi Zhang (ORCID: https://orcid.org/0000-0002-1189-2118)
- Lina Li (ORCID: https://orcid.org/0000-0001-6085-7733)
- Wei Dong (ORCID: https://orcid.org/0000-0002-8107-3900)
- Xiaolei Liu (ORCID: https://orcid.org/0000-0002-6307-4475)
- Kaiyue Zhang (ORCID: https://orcid.org/0000-0002-9906-9053)
- Lei Dai (ORCID: https://orcid.org/0000-0002-4469-7386)
- Chang Xu (ORCID: https://orcid.org/0000-0002-5659-6654)
Institutions
- Johannes Gutenberg University Mainz (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Xianning Central Hospital (CN)
- Hubei Provincial Hospital of Traditional Chinese Medicine (CN)
- Hubei Provincial Center for Disease Control and Prevention (CN)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
- University of Pecs (HU)
Publication Details
- Journal
- Diabetes
- Published
- 2025-08-15
- DOI
- https://doi.org/10.2337/db25-0077
- Citations
- 1
- Primary Topic
- Lipoproteins and Cardiovascular Health
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- National Natural Science Foundation of China