ArticleThe Journal of clinical investigation2022
IP3 receptor orchestrates maladaptive vascular responses in heart failure.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
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- The role of IPPflugers Archiv : European journal of physiology · 2026Review
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- FTO-Eci1 Axis Mediates Exercise-Induced Cardioprotection in Pressure Overload Mice.Biomolecules · 2026Article
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- NEXN regulates vascular smooth muscle cell phenotypic switching and neointimal hyperplasia.JCI insight · 2025Article
- Longevity mechanisms in cardiac aging: exploring calcium dysregulation and senescence.Biogerontology · 2025Review
- Article
- Inositol 1,4,5-Trisphosphate Receptors Regulate Vascular Smooth Muscle Cell Proliferation and Neointima Formation in Mice.Journal of the American Heart Association · 2024Article
- A structure-based computational model of IPBiophysical journal · 2024Article
- Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Editorial: Mitochondrial remodeling and dynamic inter-organellar contacts in cardiovascular physiopathology-Volume II.Frontiers in cell and developmental biology · 2023Article
- Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19.The Journal of pharmacology and experimental therapeutics · 2023Article
- IP3 receptor orchestrates maladaptive vascular responses in heart failure.The Journal of clinical investigation · 2022Article
- Diabetes and restenosis.Cardiovascular diabetology · 2022Review
- Vascular dysfunction in HFpEF: Potential role in the development, maintenance, and progression of the disease.Frontiers in cardiovascular medicine · 2022Review
- Cardiac Remodeling After Myocardial Infarction: Functional Contribution of microRNAs to Inflammation and Fibrosis.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Patients with heart failure (HF) have augmented vascular tone, which increases cardiac workload, impairing ventricular output and promoting further myocardial dysfunction. The molecular mechanisms underlying the maladaptive vascular responses observed in HF are not fully understood. Vascular smooth muscle cells (VSMCs) control vasoconstriction via a Ca2+-dependent process, in which the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) on the sarcoplasmic reticulum (SR) plays a major role. To dissect the mechanistic contribution of intracellular Ca2+ release to the increased vascular tone observed in HF, we analyzed the remodeling of IP3R1 in aortic tissues from patients with HF and from controls. VSMC IP3R1 channels from patients with HF and HF mice were hyperphosphorylated by both serine and tyrosine kinases. VSMCs isolated from IP3R1VSMC-/- mice exhibited blunted Ca2+ responses to angiotensin II (ATII) and norepinephrine compared with control VSMCs. IP3R1VSMC-/- mice displayed significantly reduced responses to ATII, both in vivo and ex vivo. HF IP3R1VSMC-/- mice developed significantly less afterload compared with HF IP3R1fl/fl mice and exhibited significantly attenuated progression toward decompensated HF and reduced interstitial fibrosis. Ca2+-dependent phosphorylation of the MLC by MLCK activated VSMC contraction. MLC phosphorylation was markedly increased in VSMCs from patients with HF and HF mice but reduced in VSMCs from HF IP3R1VSMC-/- mice and HF WT mice treated with ML-7. Taken together, our data indicate that VSMC IP3R1 is a major effector of increased vascular tone, which contributes to increased cardiac afterload and decompensation in HF.
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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 Socratic graph.