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ResearchIn-Press PreviewAgingVascular biology
Open Access | 10.1172/JCI165933
1Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
2Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Blatimore, United States of America
3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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1Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
2Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Blatimore, United States of America
3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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2Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Blatimore, United States of America
3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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2Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Blatimore, United States of America
3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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3Laboratory of Genetics and Genomic, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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1Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
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5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
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6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
8Department of Biochemistry, Albert Einstein College of Medcine, Bronx, United States of America
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4Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
5Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
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6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
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6Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, United States of America
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7Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States of America
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Published April 25, 2023 - More info
Senescent vascular smooth muscle cells (VSMCs) accumulate in the vasculature with age and tissue damage, and secrete factors that promote atherosclerotic plaque vulnerability and disease. Here, we report increased levels and activity of dipeptidyl peptidase 4 (DPP4), a serine protease, in senescent VSMCs. Analysis of the conditioned media from senescent VSMCs revealed a unique senescence-associated secretory phenotype (SASP) signature comprising many complement and coagulation factors; silencing or inhibiting DPP4 reduced these factors and increased cell death. Serum samples from persons with high risk for cardiovascular disease contained high levels of DPP4-regulated complement and coagulation factors. Importantly, DPP4 inhibition reduced senescent cell burden and coagulation and improved plaque stability, while single-cell resolution of senescent VSMCs reflected the senomorphic and senolytic effects of DPP4 inhibition in murine atherosclerosis. We propose that DPP4-regulated factors could be exploited therapeutically to reduce senescent cell function, reverse senohemostasis, and improve vascular disease.