ArticleAmerican journal of physiology. Heart and circulatory physiology2015
Increased coagulation and suppressed generation of activated protein C in aged mice during intra-abdominal sepsis.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Mouse models for post-sepsis syndrome: a comparison of cecal slurry injection model versus two cecal ligation and puncture models.Frontiers in medicine · 2026Article
- Article
- Impact of age on the host response to sepsis in a murine model of fecal-induced peritonitis.Intensive care medicine experimental · 2024Article
- PAI-1 as a critical factor in the resolution of sepsis and acute kidney injury in old age.Frontiers in cell and developmental biology · 2023Article
- Association between age and the host response in critically ill patients with sepsis.Critical care (London, England) · 2022Article
- Visceral fat-specific regulation of plasminogen activator inhibitor-1 in aged septic mice.Journal of cellular physiology · 2022Article
- Divergent Sepsis Pathophysiology in Older Adults.Antioxidants & redox signaling · 2021Review
- Aged IRF3-KO Mice are Protected from Sepsis.Journal of inflammation research · 2021Article
- Role of the activation peptide in the mechanism of protein C activation.Scientific reports · 2020Article
- Clots retrieved by mechanical thrombectomy from acute ischemic stroke patients show no evidence of bacteria.Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences · 2019Article
- Age-dependent cardiovascular effects of sepsis in a murine model of cecal ligation and puncture: implications for the design of interventional studies.American journal of physiology. Heart and circulatory physiology · 2018Article
- Rational Design of Protein C Activators.Scientific reports · 2017Article
- Fibrinogen Is at the Interface of Host Defense and Pathogen Virulence in Staphylococcus aureus Infection.Seminars in thrombosis and hemostasis · 2016Review
- Could Biomarkers Direct Therapy for the Septic Patient?The Journal of pharmacology and experimental therapeutics · 2016Review
- Age Is Associated With the Efficacy of Anticoagulant Therapies Against Sepsis-Induced Disseminated Intravascular Coagulation.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Sepsis is a life-threatening clinical condition that is particularly serious among the elderly who experience considerably higher mortality rates compared with younger patients. Using a sterile endotoxemia model, we previously reported age-dependent mortality in conjunction with enhanced coagulation and insufficient levels of anti-coagulant factor activated protein C (aPC). The purpose of the present study was to further investigate the mechanisms for age-dependent coagulation and aPC insufficiency during experimental sepsis. Intra-abdominal sepsis was induced by cecal ligation and puncture (CLP) using 21 or 16 gauge (G) needles (double-puncture) on young (4 to 6 mo old) and aged (20 to 25 mo old) male C57BL/6 mice. When compared with young mice, aged mice showed significantly increased mortality (92% vs. 28%), systemic inflammation, and coagulation in the lung and kidney after 21G CLP. Young mice with more severe CLP (16G) showed a mortality rate and inflammation equivalent to aged mice with 21G CLP; however, enhanced coagulation and kidney dysfunction were significant only in the aged. In young mice, increased levels of aPC after CLP were coupled with reduced levels of protein C (PC), suggesting the conversion of PC to aPC; however, PC and aPC levels remained unchanged in aged mice, indicating a lack of PC to aPC conversion. Activation of fibrinolysis, determined by plasma d-dimer levels, was similar regardless of age or CLP severity, and plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, showed severity-dependent induction independent of age. These results suggest that enhanced coagulation in aged mice during sepsis is due to dysfunction of the PC activation mechanism.
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