ArticleAging cell2026
The Senokine Gas6 Promotes Aortic Valve Calcification Through CaMKII-DRP1-Mediated Terminal Scission of Mitochondrial-Derived Vesicles.
Yaoyu Zhang, Jialiang Zhang, Yanjiani Xu, Wenhua Lei, Fei Xu, Junli Li, Zisong Wei, Bo Su, Shuang Liu, Jing Zhou and 8 more
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In one paragraphArticle in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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18 authors.
Yaoyu ZhangLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.ORCID https://orcid.org/0009-0001-3263-3617 Jialiang ZhangLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.ORCID https://orcid.org/0000-0001-7737-0323 Yanjiani XuLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.ORCID https://orcid.org/0000-0002-7765-514X Fei XuLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Junli LiLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Bo SuCore Facilities of West China Hospital, Chengdu, Sichuan, China.
Shuang LiuLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Jing ZhouLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Junpeng RanLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.ORCID https://orcid.org/0009-0003-1381-6797 Weiya LiLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Tuerhongjiang TuerdiLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.ORCID https://orcid.org/0009-0000-7101-351X Fangyang HuangLaboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, People's Republic of China.ORCID https://orcid.org/0000-0002-3049-2996 Funding
Fundamental Research Funds for the Central UniversitiesNational Natural Science Foundation of China 82170375National Natural Science Foundation of China 82500455National Natural Science Foundation of China U23A20395Natural Science Foundation of Sichuan Province 2026NSFSC0552Noncommunicable Chronic Diseases-National Science and Technology Major Project 2026ZD0554300
6 · The paper itselfAbstract
Calcific aortic valve disease (CAVD) is an age-associated valvular disorder in which calcification expands from discrete foci into adjacent tissue. We investigated whether mitochondrial-derived vesicles (MDVs) released by human valvular interstitial cells (hVICs) exert pro-calcific effects on recipient cells and how MDV release is regulated. Using ex vivo hemodynamic perfusion of human CAVD tissue, multi-omics profiling, live-cell single-organelle tracking, MDV transfer assays, and in vivo Gas6 deletion, we found that calcifying hVICs hypersecreted MDVs that exerted pro-calcific effects in recipient hVICs. High-resolution imaging showed that mitochondria remodeled into donut-shaped structures under pro-osteogenic conditions; these structures served as physical platforms for MDV budding. Human CAVD valve tissues and hVICs treated with pro-osteogenic medium also exhibited senescence-associated features. Multi-omics profiling identified growth arrest-specific 6 (Gas6), a senokine, among 36 concordantly upregulated candidates. Functional analyzes showed that Gas6 promoted terminal MDV scission while leaving donut-shaped mitochondrial precursor formation intact. Mechanistically, Gas6 promoted intracellular Ca
Indexed as
Aortic ValveAortic Valve StenosisCalcinosisCalcium-Calmodulin-Dependent Protein Kinase Type 2DynaminsIntercellular Signaling Peptides and ProteinsMitochondriaAnimalsGrowth Arrest-Specific Protein 6HumansCalcium-Calmodulin-Dependent Protein Kinase Type 2DynaminsGrowth Arrest-Specific Protein 6Intercellular Signaling Peptides and Proteinsaortic valve calcificationcalcific aortic valve diseaseGas6mitochondrial‐derived vesicles
Identifiers
PMID42902865
PMCPMC13684317
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