ArticleAging cell2015
Cathepsin K knockout alleviates aging-induced cardiac dysfunction.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Transcutaneous auricular vagus nerve stimulation alleviates chronic heart failure by targeting cathepsin K/p53-mediated ferroptosis.Biology direct · 2026Article
- Targeting Cathepsin K to Accelerate Diabetic Wound Healing.ACS pharmacology & translational science · 2025Article
- The onset and the development of cardiometabolic aging: an insight into the underlying mechanisms.Frontiers in pharmacology · 2024Review
- Recent Advances in the Mechanisms of Cell Death and Dysfunction in Doxorubicin Cardiotoxicity.Reviews in cardiovascular medicine · 2023Review
- Article
- The role of cellular senescence in cardiac disease: basic biology and clinical relevance.Nature reviews. Cardiology · 2022Review
- Lack of food intake during shift work alters the heart transcriptome and leads to cardiac tissue fibrosis and inflammation in rats.BMC biology · 2022Article
- Genome-Wide Gene Expression Profiles Reveal Distinct Molecular Characteristics of the Goose Granulosa Cells.Frontiers in genetics · 2021Article
- LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis.Frontiers in pharmacology · 2021Article
- Article
- Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation.JCI insight · 2020Article
- Cysteinyl cathepsins in cardiovascular diseases.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- Article
- Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice.Stem cells international · 2020Article
- Cathepsin K: The Action in and Beyond Bone.Frontiers in cell and developmental biology · 2020Review
- Exogenous Hydrogen Sulfide Ameliorates Diabetic Myocardial Fibrosis by Inhibiting Cell Aging Through SIRT6/AMPK Autophagy.Frontiers in pharmacology · 2020Article
- Forkhead box O3 protects the heart against paraquat-induced aging-associated phenotypes by upregulating the expression of antioxidant enzymes.Aging cell · 2019Article
- Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone.Journal of cancer research and clinical oncology · 2019Article
- Endogenous reduction of miR-185 accelerates cardiac function recovery in mice following myocardial infarction via targeting of cathepsin K.Journal of cellular and molecular medicine · 2019Article
- Cardiomyocyte-specific disruption of Cathepsin K protects against doxorubicin-induced cardiotoxicity.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects against pressure overload-induced cardiac hypertrophy and contractile dysfunction. Here we test the hypothesis that cathepsin K knockout alleviates age-dependent decline in cardiac function. Cardiac geometry, contractile function, intracellular Ca(2+) properties, and cardiomyocyte apoptosis were evaluated using echocardiography, fura-2 technique, immunohistochemistry, Western blot and TUNEL staining, respectively. Aged (24-month-old) mice exhibited significant cardiac remodeling (enlarged chamber size, wall thickness, myocyte cross-sectional area, and fibrosis), decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca(2+) release compared to young (6-month-old) mice, which were attenuated in the cathepsin K knockout mice. Cellular markers of senescence, including cardiac lipofuscin, p21 and p16, were lower in the aged-cathepsin K knockout mice compared to their wild-type counterpart. Mechanistically, cathepsin K knockout mice attenuated an age-induced increase in cardiomyocyte apoptosis and nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). In cultured H9c2 cells, doxorubicin stimulated premature senescence and apoptosis. Silencing of cathepsin K blocked the doxorubicin-induced translocation of AIF from the mitochondria to the nuclei. Collectively, these results suggest that cathepsin K knockout attenuates age-related decline in cardiac function via suppressing caspase-dependent and caspase-independent apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.