ArticleSignal transduction and targeted therapy2023
Astragaloside IV derivative HHQ16 ameliorates infarction-induced hypertrophy and heart failure through degradation of lncRNA4012/9456.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The interventional effect of astragaloside IV on rodent models of myocardial fibrosis: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Effect of Qishen Yiqi Dripping Pill on Clinical Outcomes in Patients with Ischemic Heart Failure: A Post-Hoc Analysis of the CACT-IHF Randomized Trial.Drug design, development and therapy · 2025Trial
- Trilobatin Ameliorates Myocardial Hypertrophy by Enhancing Mitophagy Through Activation of the Sentrin-Specific Protease 1/Sirtuin 3 Axis in Spontaneously Hypertensive Rats.Phytotherapy research : PTR · 2026Article
- Ferroptosis-driven immune remodeling in heart failure: the central role of macrophage reprogramming and impaired efferocytosis.Journal of nanobiotechnology · 2026Review
- Astragaloside IV Reduces Sorafenib-Induced Cardiotoxicity by Inhibiting Apoptosis Through the STAT3/HIF-1α/Bcl-2 Signaling Pathway.International journal of molecular sciences · 2026Article
- Research Progress on the Biological Function, Disease-Driving Mechanism and Clinical Targeting Strategies of G3BP2.Molecules (Basel, Switzerland) · 2026Review
- Cycloastragenol Derivatives Improve Tyrosine Metabolism, Regulate TLR4/NF-κB/TERT Signaling Pathways, and Inhibit MPTP Induced Neuroinflammation and PD Symptoms.CNS neuroscience & therapeutics · 2026Article
- Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Design of RGD-functionalized GSH-responsive pegylated polymeric protacs for selective BRD4 degradation and EndMT-driven cardiac fibrosis inhibition.Journal of nanobiotechnology · 2026Article
- Mangiferin inhibits cGAS-STING pathway-related inflammation via Nrf2 activation to protect against sepsis-induced heart injury.Chinese medicine · 2026Article
- Mixture design optimization of salvianolic acid B, tanshinone IIA, butein, and formononetin fromFrontiers in pharmacology · 2026Article
- Astragaloside IV inhibits MAPK pathway and promotes mitochondrial autophagy in rats with heart failure.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Bibliometric Analysis of Research on Traditional Chinese Medicine Treatment of Myocardial Infarction from 2007 to 2024 Based on the Web of Science Database.Current medicinal chemistry · 2026Article
- Gastrin ameliorates heart failure and suppresses myocardial remodeling via the JAK2/STAT3 and ERK1/2 pathways.PloS one · 2026Article
- Astragaloside IV prevents calpain-1-mediated cardiac hypertrophy and fibrosis induced by diabetes.Frontiers in cardiovascular medicine · 2026Article
- The silent dialogue between cells: regulatory roles of non-coding RNAs in cardiovascular disease.Frontiers in cell and developmental biology · 2026Review
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- Multitarget mechanisms and clinical integration of traditional Chinese medicine in cardiac rehabilitation: a narrative review.Frontiers in cardiovascular medicine · 2026Review
- Electroacupuncture Protects Against Post-MI Heart Failure Through Autonomic Regulation and α7nAChR Activation.Cardiology research and practice · 2026Article
- Targeting mitochondrial autophagy for anti-aging.Cell death discovery · 2025Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction (MI) heart failure (HF). Here, we report a novel small molecule HHQ16, an optimized derivative of astragaloside IV, which effectively reversed infarction-induced myocardial remodeling and improved cardiac function by directly acting on the cardiomyocyte to reverse hypertrophy. The effect of HHQ16 was associated with a strong inhibition of a newly discovered Egr2-affiliated transcript lnc9456 in the heart. While minimally expressed in normal mouse heart, lnc9456 was dramatically upregulated in the heart subjected to left anterior descending coronary artery ligation (LADL) and in cardiomyocytes subjected to hypertrophic stimulation. The critical role of lnc9456 in cardiomyocyte hypertrophy was confirmed by specific overexpression and knockout in vitro. A physical interaction between lnc9456 and G3BP2 increased NF-κB nuclear translocation, triggering hypertrophy-related cascades. HHQ16 physically bound to lnc9456 with a high-affinity and induced its degradation. Cardiomyocyte-specific lnc9456 overexpression induced, but knockout prevented LADL-induced, cardiac hypertrophy and dysfunction. HHQ16 reversed the effect of lnc9456 overexpression while lost its protective role when lnc9456 was deleted, further confirming lnc9456 as the bona fide target of HHQ16. We further identified the human ortholog of lnc9456, also an Egr2-affiliated transcript, lnc4012. Similarly, lnc4012 was significantly upregulated in hypertrophied failing hearts of patients with dilated cardiomyopathy. HHQ16 also specifically bound to lnc4012 and caused its degradation and antagonized its hypertrophic effects. Targeted degradation of pathological increased lnc4012/lnc9456 by small molecules might serve as a novel promising strategy to regress infarction-induced cardiac hypertrophy and HF.
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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.