ArticleCirculation research2022
Activated Protein C Strengthens Cardiac Tolerance to Ischemic Insults in Aging.
Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting PAR1 biased signaling with parmodulin reduces thromboinflammation and acute lung injury in sickle cell disease.Blood advances · 2026Article
- Microrna363-5p targets thrombospondin3 to regulate pathological cardiac remodeling.Molecular and cellular biochemistry · 2025Article
- Endothelial protein C receptor promotes retinal neovascularization through heme catabolism.Nature communications · 2025Article
- Identification of endothelial protein C receptor as a novel druggable agonistic target for reendothelialization promotion and thrombosis prevention of eluting stent.Bioactive materials · 2024Article
- Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Melatonin alleviates aging-related heart failure through melatonin receptor 1A/B knockout in mice.Heliyon · 2024Article
- Platelets at the intersection of inflammation and coagulation in the APC-mediated response to myocardial ischemia/reperfusion injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- EPCR shedding light on sickle nephropathy.Blood · 2024Article
- An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.Journal of thrombosis and haemostasis : JTH · 2024Article
- Biased agonism of protease-activated receptor-1 regulates thromboinflammation in murine sickle cell disease.Blood advances · 2024Article
- A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation.Metabolism: clinical and experimental · 2024Article
- Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer's disease by activated protein C.Aging · 2024Article
- Administration of metformin rescues age-related vulnerability to ischemic insults through mitochondrial energy metabolism.Biochemical and biophysical research communications · 2023Article
- Thrombin-mediated activation of PAR1 enhances doxorubicin-induced cardiac injury in mice.Blood advances · 2023Article
- Article
- Activated protein C in epilepsy pathophysiology.Frontiers in neuroscience · 2023Review
- Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.International journal of molecular and cellular medicine · 2023Review
- The APC-EPCR-PAR1 axis in sickle cell disease.Frontiers in medicine · 2023Review
- Sirtuin 1 aggravates hypertrophic heart failure caused by pressure overload via shifting energy metabolism.Biochemical and biophysical research communications · 2022Article
- Targeting on Nrf2/Sesn2 Signaling to Rescue Cardiac Dysfunction during High-Fat Diet-Induced Obesity.Cells · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAPC (activated protein C) is a plasma serine protease with anticoagulant and anti-inflammatory activities. EPCR (Endothelial protein C receptor) is associated with APC's activity and mediates its downstream signaling events. APC exerts cardioprotective effects during ischemia and reperfusion (I/R). This study aims to characterize the role of the APC-EPCR axis in ischemic insults in aging.
methodsYoung (3-4 months) and aged (24-26 months) wild-type C57BL/6J mice, as well as EPCR point mutation (EPCR
resultsThe results demonstrated that cardiac I/R reduces APC activity, and the APC activity was impaired in the aged versus young hearts possibly attributable to the declined EPCR level with aging. Serum EPCR measurement showed that I/R triggered the shedding of membrane EPCR into circulation, while administration of APC attenuated the I/R-induced EPCR shedding in both young and aged hearts. Subsequent echocardiography showed that APC and APC-2Cys but not APC-E170A ameliorated cardiac dysfunction during I/R in both young and aged mice. Importantly, APC elevated the resistance of the aged heart to ischemic insults through stabilizing EPCR. However, all these cardioprotective effects of APC were blunted in the EPCR
conclusionsI/R stress causes shedding of the membrane EPCR in the heart, and administration of APC prevents I/R-induced cardiac EPCR shedding that is critical for limiting cardiac damage in aging.
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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.