ArticleBasic research in cardiology2024
Pinacidil ameliorates cardiac microvascular ischemia-reperfusion injury by inhibiting chaperone-mediated autophagy of calreticulin.
Article in Basic research in cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A Comprehensive Review on Cardioprotective Biological Properties of Crataegus orientalis in Post-COVID-19 Pandemic Cardiovascular Disorders.Molecular nutrition & food research · 2026Review
- Programmed Cell Death of Endothelial Cells in Ischemic Heart Disease: Mechanism and Potential Cell and Gene Therapeutic Prospects.Bioengineering (Basel, Switzerland) · 2026Review
- TrxR2 Lactylation Facilitates Mitochondrial Protection and Endothelial Ferroptosis Resistance in Diabetic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chaperone-Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondria-associated endoplasmic reticulum membranes: Emerging regulators of cardiac microvascular ischemia/reperfusion injury (Review).International journal of molecular medicine · 2026Review
- Article
- Mechanisms of mitochondrial dysfunction and protective strategies in skin flap ischemia-reperfusion injury.Frontiers in pharmacology · 2026Review
- Dihydromyricetin confers protection against myocardial ischemia-reperfusion injury by inhibiting ferroptosis through direct targeting of PPARα.Frontiers in pharmacology · 2026Article
- Unlocking Neuroprotection: Potassium Channel Openers in Alzheimer's Disease.Current Alzheimer research · 2026Review
- Continuous pressure exacerbates ischemia-reperfusion injury in minipigs through the AKT/eNOS signaling pathway.European journal of medical research · 2025Article
- Helicobacter hepaticus promotes hepatic steatosis through CdtB-induced mitochondrial stress and lipid metabolism reprogramming.Nature communications · 2025Article
- Advances in Pathophysiology and Novel Therapeutic Strategies for Coronary No-Reflow Phenomenon.Biomedicines · 2025Review
- Brazilin alleviates acute lung injury via inhibition of ferroptosis through the SIRT3/GPX4 pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- Gypensapogenin I alleviates PANoptosis, ferroptosis, and oxidative stress in myocardial ischemic-reperfusion injury by targeting the NOX2/AMPK pathway.Frontiers in cell and developmental biology · 2025Article
- Multiple regulatory mechanisms, functions and therapeutic potential of chaperone-mediated autophagy.Theranostics · 2025Review
- Nutritional strategies in abdominal surgery: the potential of ketogenic diet.Frontiers in nutrition · 2025Review
- Decoding interaction between mitochondria and endoplasmic reticulum in ischemic myocardial injury: targeting natural medicines.Frontiers in pharmacology · 2025Review
- Article
- Repositioning pinacidil and its anticonvulsant and anxiolytic properties in murine models.Scientific reports · 2024Article
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Calcium overload is the key trigger in cardiac microvascular ischemia-reperfusion (I/R) injury, and calreticulin (CRT) is a calcium buffering protein located in the endoplasmic reticulum (ER). Additionally, the role of pinacidil, an antihypertensive drug, in protecting cardiac microcirculation against I/R injury has not been investigated. Hence, this study aimed to explore the benefits of pinacidil on cardiac microvascular I/R injury with a focus on endothelial calcium homeostasis and CRT signaling. Cardiac vascular perfusion and no-reflow area were assessed using FITC-lectin perfusion assay and Thioflavin-S staining. Endothelial calcium homeostasis, CRT-IP3Rs-MCU signaling expression, and apoptosis were assessed by real-time calcium signal reporter GCaMP8, western blotting, and fluorescence staining. Drug affinity-responsive target stability (DARTS) assay was adopted to detect proteins that directly bind to pinacidil. The present study found pinacidil treatment improved capillary density and perfusion, reduced no-reflow and infraction areas, and improved cardiac function and hemodynamics after I/R injury. These benefits were attributed to the ability of pinacidil to alleviate calcium overload and mitochondria-dependent apoptosis in cardiac microvascular endothelial cells (CMECs). Moreover, the DARTS assay showed that pinacidil directly binds to HSP90, through which it inhibits chaperone-mediated autophagy (CMA) degradation of CRT. CRT overexpression inhibited IP3Rs and MCU expression, reduced mitochondrial calcium inflow and mitochondrial injury, and suppressed endothelial apoptosis. Importantly, endothelial-specific overexpression of CRT shared similar benefits with pinacidil on cardiovascular protection against I/R injury. In conclusion, our data indicate that pinacidil attenuated microvascular I/R injury potentially through improving CRT degradation and endothelial calcium overload.
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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.