ArticlePloS one2018
Tongxinluo attenuates reperfusion injury in diabetic hearts by angiopoietin-like 4-mediated protection of endothelial barrier integrity via PPAR-α pathway.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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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
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Efficacy and safety of combining commercial Chinese polyherbal preparation with conventional medicine in the treatment of coronary microvascular disease: a systematic review and network meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Efficacy and safety of Tongxinluo capsules combined with conventional therapy for acute myocardial infarction: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Trial
- Comparative efficacy and safety of oral Chinese patent medicines combined with conventional therapy for coronary heart disease complicated by diabetes: a systematic review and network meta-analysis.Frontiers in cardiovascular medicine · 2026Review
- Tongxinluo alleviates myocardial ischemia-reperfusion injury by inhibiting the pyroptosis of endothelial cells via the NLRP3/Caspase-1/GSDMD signaling pathway.Journal of molecular histology · 2025Article
- Review
- The role and mechanisms of microvascular damage in the ischemic myocardium.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease.World journal of diabetes · 2023Article
- Tongxinluo-pretreated mesenchymal stem cells facilitate cardiac repair via exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway.Stem cell research & therapy · 2022Article
- Junctional Adhesion Molecules: Potential Proteins in Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- Protective Effect and Mechanism of Traditional Chinese Medicine on Myocardial Ischemia Reperfusion Injury.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Pemafibrate suppresses oxidative stress and apoptosis under cardiomyocyte ischemia-reperfusion injury in type 1 diabetes mellitus.Experimental and therapeutic medicine · 2021Article
- PPAROxidative medicine and cellular longevity · 2021Article
- China Tongxinluo Study for myocardial protection in patients with Acute Myocardial Infarction (CTS-AMI): Rationale and design of a randomized, double-blind, placebo-controlled, multicenter clinical trial.American heart journal · 2020Article
- Skeletal Muscle Angiopoietin-Like Protein 4 and Glucose Metabolism in Older Adults after Exercise and Weight Loss.Metabolites · 2020Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveEndothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity. METHODS AND
resultsI/R injury was created by coronary ligation in ZDF diabetic and non-diabetic control rats. The animals were anesthetized and randomized to sham operation or I/R injury with or without the exposure to insulin, rhAngptl4, TXL, Angptl4 siRNA, and the PPAR-α inhibitor MK886. Tongxinluo, insulin and rhAngptl4 have the similar protective effect on diabetic hearts against I/R injury. In I/R-injured diabetic hearts, TXL treatment remarkably reduced the infarct size, and protected endothelial barrier integrity demonstrated by decreased endothelial cells apoptosis, microvascular permeability, and myocardial hemorrhage, fortified tight junction, and upregulated expression of JAM-A, integrin-α5, and VE-cadherin, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with siRNA interference and inhibition of PPAR-α with MK886 partially diminished these beneficial effects of TXL and rhAngptl4. TXL induced the expression of Angptl4 in I/R-injured diabetic hearts, and was canceled by Angptl4 siRNA and MK886. TXL treatment increased myocardial PPAR-α activity, and was abolished by MK886 but not by Angptl4 siRNA.
conclusionsTXL protects diabetic hearts against I/R injury by activating Angptl4-mediated restoration of endothelial barrier integrity via the PPAR-α pathway.
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