ArticleCardiovascular research2019
Endothelial and cardiomyocyte PI3Kβ divergently regulate cardiac remodelling in response to ischaemic injury.
Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction.Cardiovascular research · 2026Article
- Screening and characterization of pro-angiogenic peptides fromFrontiers in pharmacology · 2026Article
- Deficiency in N-cadherin-Akt3 signaling impairs the blood-brain barrier.Cell reports · 2025Article
- Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice.Chinese journal of integrative medicine · 2024Article
- Shear stress and pathophysiological PI3K involvement in vascular malformations.The Journal of clinical investigation · 2024Review
- The RISK pathway leading to mitochondria and cardioprotection: how everything started.Basic research in cardiology · 2023Review
- Gene expression patterns and related pathways in the hearts of rhesus monkeys subjected to prolonged myocardial ischemia.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans.Journal of the American Heart Association · 2022Article
- Role of PI3K/Akt signaling pathway in cardiac fibrosis.Molecular and cellular biochemistry · 2021Review
- The Human Explanted Heart Program: A translational bridge for cardiovascular medicine.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Low-Level Nanog Expression in the Regulation of Quiescent Endothelium.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020Review
- PI3Kα in cardioprotection: Cytoskeleton, late NaChannels (Austin, Tex.) · 2019Review
- Revisiting PI3-kinase signalling in angiogenesis.Vascular biology (Bristol, England) · 2019Review
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11 authors at 4 institutions in 3 countries.
Funding
Abstract
aimsCardiac remodelling in the ischaemic heart determines prognosis in patients with ischaemic heart disease (IHD), while enhancement of angiogenesis and cell survival has shown great potential for IHD despite translational challenges. Phosphoinositide 3-kinase (PI3K)/Akt signalling pathways play a critical role in promoting angiogenesis and cell survival. However, the effect of PI3Kβ in the ischaemic heart is poorly understood. This study investigates the role of endothelial and cardiomyocyte (CM) PI3Kβ in post-infarct cardiac remodelling. METHODS AND
resultsPI3Kβ catalytic subunit-p110β level was increased in infarcted murine and human hearts. Using cell type-specific loss-of-function approaches, we reported novel and distinct actions of p110β in endothelial cells (ECs) vs. CMs in response to myocardial ischaemic injury. Inactivation of endothelial p110β resulted in marked resistance to infarction and adverse cardiac remodelling with decreased mortality, improved systolic function, preserved microvasculature, and enhanced Akt activation. Cultured ECs with p110β knockout or inhibition displayed preferential PI3Kα/Akt/endothelial nitric oxide synthase signalling that consequently promoted protective signalling and angiogenesis. In contrast, mice with CM p110β-deficiency exhibited adverse post-infarct ventricular remodelling with larger infarct size and deteriorated cardiac function, which was due to enhanced susceptibility of CMs to ischaemia-mediated cell death. Disruption of CM p110β signalling compromised nuclear p110β and phospho-Akt levels leading to perturbed gene expression and elevated pro-cell death protein levels, increasing the susceptibility to CM death. A similar divergent response of PI3Kβ endothelial and CM mutant mice was seen using a model of myocardial ischaemia-reperfusion injury.
conclusionThese data demonstrate novel, differential, and cell-specific functions of PI3Kβ in the ischaemic heart. While the loss of endothelial PI3Kβ activity produces cardioprotective effects, CM PI3Kβ is protective against myocardial ischaemic injury.
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