ArticleJournal of molecular and cellular cardiology2016
Protease-activated receptor 4 deficiency offers cardioprotection after acute ischemia reperfusion injury.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- SLFN11 enhances cisplatin sensitivity in pediatric cancer via activation of stress-response and suppression of survival pathways.British journal of cancer · 2026Article
- PAR for the course - protease-activated receptor 4 protects the brain from hemorrhage.Research and practice in thrombosis and haemostasis · 2026Article
- Article
- Elevated protease-activated receptor 4 (PAR4) gene expression in Alzheimer's disease predicts cognitive decline.Neurobiology of aging · 2024Article
- Detrimental interactions of hypoxia and complement MASP-1 in endothelial cells as a model for atherosclerosis-related diseases.Scientific reports · 2024Article
- Platelets Induce Cell Apoptosis of Cardiac Cells via FasL after Acute Myocardial Infarction.Biomedicines · 2024Article
- Discovery of Protease-Activated Receptor 4 (PAR4)-Tethered Ligand Antagonists Using Ultralarge Virtual Screening.ACS pharmacology & translational science · 2024Article
- Role of protease-activated receptor 4 in mouse models of acute and chronic kidney injury.American journal of physiology. Renal physiology · 2024Article
- PAR4 Inhibition Reduces Coronary Artery Atherosclerosis and Myocardial Fibrosis in SR-B1/LDLR Double Knockout Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Species Differences in Platelet Protease-Activated Receptors.International journal of molecular sciences · 2023Review
- Platelets in Myocardial Ischemia/Reperfusion Injury.Hamostaseologie · 2023Review
- Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure.The Journal of clinical investigation · 2023Article
- Platelets modulate cardiac remodeling via the collagen receptor GPVI after acute myocardial infarction.Frontiers in immunology · 2023Article
- Article
- PAR-Induced Harnessing of EZH2 to β-Catenin: Implications for Colorectal Cancer.International journal of molecular sciences · 2022Article
- Article
- Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The "Circulating Wound" Model.International journal of molecular sciences · 2021Review
- PAR-4/CaCardiovascular diabetology · 2021Article
- Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently.Circulation research · 2021Article
- Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Protease-activated receptor (PAR)4 is a low affinity thrombin receptor with less understood function relative to PAR1. PAR4 is involved in platelet activation and hemostasis, but its specific actions on myocyte growth and cardiac function remain unknown. This study examined the role of PAR4 deficiency on cardioprotection after myocardial ischemia-reperfusion (IR) injury in mice. When challenged by in vivo or ex vivo IR, PAR4 knockout (KO) mice exhibited increased tolerance to injury, which was manifest as reduced infarct size and a more robust functional recovery compared to wild-type mice. PAR4 KO mice also showed reduced cardiomyocyte apoptosis and putative signaling shifts in survival pathways in response to IR. Inhibition of PAR4 expression in isolated cardiomyocytes by shRNA offered protection against thrombin and PAR4-agonist peptide-induced apoptosis, while overexpression of wild-type PAR4 significantly enhanced the susceptibility of cardiomyocytes to apoptosis, even under low thrombin concentrations. Further studies implicate Src- and epidermal growth factor receptor-dependent activation of JNK on the proapoptotic effect of PAR4 in cardiomyocytes. These findings reveal a pivotal role for PAR4 as a regulator of cardiomyocyte survival and point to PAR4 inhibition as a therapeutic target offering cardioprotection after acute IR injury.
Indexed as
Identifiers
What OpenQuestion holds
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.