Cell death in the pathogenesis and progression of heart failure

Marı́n-Garcı́a, José

doi:10.1007/s10741-016-9538-7

Cited by 19 publications

(11 citation statements)

References 50 publications

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“…The proliferation of CF and their conversion into MF in response to pressure overload or ischemia reperfusion injury is a key pathological step in cardiac fibrosis and a contributor to development of HF [3,6]. There is no effective therapy against cardiac fibrosis, and this has been a hurdle in developing cardiovascular drugs that inhibit the progression of heart diseases into HF [15].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac fibroblasts and cardiomyocytes are two cell types that play major roles in normal cardiac function, as well as in HF [3,4,5]. During a myocardial infarction (MI), cardiomyocytes die due to a lack of blood supply [6]. After cardiomyocyte death and the subsequent inflammatory response to clear damaged cells and debris, resident cardiac fibroblasts (CF) are activated and initiate the wound healing process [7].…”

Section: Introductionmentioning

confidence: 99%

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Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes

et al. 2019

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In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague–Dawley rats, cultured for either 24 h (cardiomyocytes) or 48 h (CF) before treatments. To isolate MF, CF were trypsinized after 48 h in culture, seeded in fresh plates and cultured for 24 h prior to treatment. All three cells were then treated for a further 24 h with a range of Rsv doses. In CF and MF, cell proliferation, viability, apoptosis assays were performed with or without Rsv treatment for 24 h. In cardiomyocytes, cell viability and apoptosis assay were performed 24 h after treatment. In separate experiments, CF was pre-incubated with estrogen, tamoxifen and fulvestrant for 30 min prior to Rsv treatment. Rsv treatment decreased proliferation of both fibroblasts and myofibroblasts. Rsv treatment also increased the proportion of dead CF and MF in a dose dependent manner. However, treatment with Rsv did not induce cell death in adult cardiomyocytes. There was an increase in the percentage of cells with condensed nuclei with Rsv treatment in both CF and MF, but not in cardiomyocytes. Treatment with estrogen, tamoxifen and fulvestrant alone or in combination with Rsv did not have any additional effects on CF survival. Our results demonstrate that treatment with Rsv can inhibit cell proliferation and induce cell death in rat CF and MF, while not affecting cardiomyocyte survival. We also demonstrated that the induction of cell death in CF with Rsv treatment was independent of estrogen receptor alpha (ERα) signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes

et al. 2019

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“…Inflammation and cell death are associated with the development of heart disease, especially under increased oxidative stress conditions, as observed in BPA treated mice 50,51 . To identify the mechanisms underlying vascular leakage and myocardial hemorrhages induced by BPA, we performed tunel assay in hearts from 8 weeks BPA treated mice, observing increased cell death, especially at the coronary endothelium and within the vascular wall, compared to CT (Fig.…”

Section: Bpa Induced Vascular Injury Is Mediated By Rip3/camkii Depenmentioning

confidence: 94%

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

Reventún¹,

Sánchez-Esteban²,

Cook³

et al. 2020

Sci Rep

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Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A. Consistent with the in vivo findings, BPA increased the necroptosis/apoptosis ratio, the expression of RIP3, and CamKII activation in endothelial cells. Necrostatin-1, an inhibitor of necroptosis, alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice. Mechanistically, silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells, while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway. Our results reveal a novel pathogenic role of BPA on the coronary circulation. BPA induces endothelial cell necroptosis, promotes the weakening of coronary vascular wall, which caused internal ventricular hemorrhages, delaying the reparative process and ultimately leading to cardiac dysfunction.

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“…Numerous preclinical studies and clinical trials have suggested that application of stem and/or progenitor cell populations to an injured heart may hold a potential to ameliorate left ventricular dysfunction caused by ischemic and dilated cardiomyopathy accompanying heart failure2345678. Among various cell types, human induced pluripotent stem cells (hiPSCs) are considered highly promising cell sources for cardiac regenerative cell therapy, because the fundamental etiology of heart failure is the result of massive loss or dysfunction of myocardial cells9, and various cardiovascular (CV) cell lineages can be scalably produced from iPSCs101112.…”

mentioning

confidence: 99%

Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue

Nakane

Masumoto

Tinney

et al. 2017

Sci Rep

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The current study describes a scalable, porous large-format engineered cardiac tissue (LF-ECT) composed of human induced pluripotent stem cells (hiPSCs) derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. We explored multiple 15 × 15 mm ECT geometries using molds with rectangular internal staggered posts (mesh, ME), without posts (plain sheet, PS), or long parallel posts (multiple linear bundles, ML) and a gel matrix containing hiPSC-derived cardiomyocytes, endothelial, and vascular mural cells matured in vitro for 14 days. ME-ECTs displayed the lowest dead cell ratio (p < 0.001) and matured into 0.5 mm diameter myofiber bundles with greater 3D cell alignment and higher active stress than PS-ECTs. Increased initial ECT cell number beyond 6 M per construct resulted in reduced cell survival and lower active stress. The 6M-ME-ECTs implanted onto 1 week post-infarct immune tolerant rat hearts engrafted, displayed evidence for host vascular coupling, and recovered myocardial structure and function with reduced scar area. We generated a larger (30 × 30 mm) ME-ECT to confirm scalability. Thus, large-format ECTs generated from hiPSC-derived cardiac cells may be feasible for large animal preclinical cardiac regeneration paradigms.

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Cell death in the pathogenesis and progression of heart failure

Cited by 19 publications

References 50 publications

Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes

Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue

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