Angiotensin II requires an intact cardiac thyrotropin-releasing hormone (TRH) system to induce cardiac hypertrophy in mouse

Diaz, Ludmila Soledad Peres; Schuman, Mariano Luis; Aisicovich, Maia; Toblli, Jorge Eduardo; Pirola, Carlos José; Landa, María Silvina; Garcı́a, Silvia

doi:10.1016/j.yjmcc.2018.09.009

Cited by 16 publications

(4 citation statements)

References 13 publications

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“…We chose the NIH/3T3 cell line for our study because it is similar to adult cardiac fibroblasts [ 33 , 60 ] and has a high mitotic rate in vitro. In addition, noncardiac fibroblasts are widely used in the production of clinical-grade exosomes for the treatment of many human diseases [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte-targeting exosomes from sulforaphane-treated fibroblasts affords cardioprotection in infarcted rats

et al. 2023

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Background Exosomes (EXOs), tiny extracellular vesicles that facilitate cell–cell communication, are being explored as a heart failure treatment, although the features of the cell source restrict their efficacy. Fibroblasts the most prevalent non-myocyte heart cells, release poor cardioprotective EXOs. A noninvasive method for manufacturing fibroblast-derived exosomes (F-EXOs) that target cardiomyocytes and slow cardiac remodeling is expected. As a cardioprotective isothiocyanate, sulforaphane (SFN)-induced F-EXOs (SFN-F-EXOs) should recapitulate its anti-remodeling properties. Methods Exosomes from low-dose SFN (3 μM/7 days)-treated NIH/3T3 murine cells were examined for number, size, and protein composition. Fluorescence microscopy, RT-qPCR, and western blot assessed cell size, oxidative stress, AcH4 levels, hypertrophic gene expression, and caspase-3 activation in angiotensin II (AngII)-stressed HL-1 murine cardiomyocytes 12 h-treated with various EXOs. The uptake of fluorescently-labeled EXOs was also measured in cardiomyocytes. The cardiac function of infarcted male Wistar rats intramyocardially injected with different EXOs (1·1012) was examined by echocardiography. Left ventricular infarct size, hypertrophy, and capillary density were measured. Results Sustained treatment of NIH/3T3 with non-toxic SFN concentration significantly enhances the release of CD81 + EXOs rich in TSG101 (Tumor susceptibility gene 101) and Hsp70 (Heat Shock Protein 70), and containing maspin, an endogenous histone deacetylase 1 inhibitor. SFN-F-EXOs counteract angiotensin II (AngII)-induced hypertrophy and apoptosis in murine HL-1 cardiomyocytes enhancing SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a) levels more effectively than F-EXOs. In stressed cardiomyocytes, SFN-F-EXOs boost AcH4 levels by 30% (p < 0.05) and significantly reduce oxidative stress more than F-EXOs. Fluorescence microscopy showed that mouse cardiomyocytes take in SFN-F-EXOs ~ threefold more than F-EXOs. Compared to vehicle-injected infarcted hearts, SFN-F-EXOs reduce hypertrophy, scar size, and improve contractility. Conclusions Long-term low-dose SFN treatment of fibroblasts enhances the release of anti-remodeling cardiomyocyte-targeted F-EXOs, which effectively prevent the onset of HF. The proposed method opens a new avenue for large-scale production of cardioprotective exosomes for clinical application using allogeneic fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Cardiomyocyte-targeting exosomes from sulforaphane-treated fibroblasts affords cardioprotection in infarcted rats

et al. 2023

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“…Functional parameters were calculated using LabChart Pro (AD Instruments) ( 72 ). For Ang II infusion, mice were implanted with subcutaneous osmotic minipumps (1002, ALZET) and infused with Ang II (2 mg/kg/d in 0.9% saline) or 0.9% saline alone for 14 days ( 73 ). For DOCA-salt studies, Sprague-Dawley rats underwent unilateral nephrectomy and were followed for 4 weeks after being implanted with 200 mg DOCA in silicone rubber, with 1% saline as drinking water, as previously described ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure

Yerra¹,

Batchu²,

Kaur³

et al. 2023

Journal of Clinical Investigation

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Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how inflammatory cells affect cardiomyocytes in the remodeling heart. Pathogenic cardiac macrophages induced an IFN response in cardiomyocytes, characterized by upregulation of the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), which posttranslationally modifies its targets through a process termed ISGylation. Cardiac ISG15 is controlled by type I IFN signaling, and ISG15 or ISGylation is upregulated in mice with transverse aortic constriction or infused with angiotensin II; rats with uninephrectomy and DOCA-salt, or pulmonary artery banding; cardiomyocytes exposed to IFNs or CD4 + T cell–conditioned medium; and ventricular tissue of humans with nonischemic cardiomyopathy. By nanoscale liquid chromatography–tandem mass spectrometry, we identified the myofibrillar protein filamin-C as an ISGylation target. ISG15 deficiency preserved cardiac function in mice with transverse aortic constriction and led to improved recovery of mouse hearts ex vivo. Metabolomics revealed that ISG15 regulates cardiac amino acid metabolism, whereas ISG15 deficiency prevented misfolded filamin-C accumulation and induced cardiomyocyte autophagy. In sum, ISG15 upregulation is a feature of pathological ventricular remodeling, and protein ISGylation is an inflammation-induced posttranslational modification that may contribute to heart failure development by altering cardiomyocyte protein turnover.

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“…Cardiac hypertrophy is characterized by myocardial fibrosis (excess deposition of extracellular matrix: ECM), capillary rarefaction, inflammation, and cellular dysfunction, which results in maladaptive ventricular remodeling (accumulation of cardiac fibroblasts) and heart failure. Maladaptive hypertrophy is induced by a sustained vascular hypertension, involving ANG II [ 48 ]. In addition, oxidative stress has emerged as a key mechanistic mediator of myocardial fibrosis [ 49 ].…”

Section: Role Of Nrf2 In Obesity-induced Cardiac Alterations and Adip...mentioning

confidence: 99%

The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors

et al. 2022

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The raising prevalence of obesity is associated with an increased risk for cardiovascular diseases (CVDs), particularly coronary artery disease (CAD), and heart failure, including atrial fibrillation, ventricular arrhythmias and sudden death. Obesity contributes directly to incident cardiovascular risk factors, including hyperglycemia or diabetes, dyslipidemia, and hypertension, which are involved in atherosclerosis, including structural and functional cardiac alterations, which lead to cardiac dysfunction. CVDs are the main cause of morbidity and mortality worldwide. In obesity, visceral and epicardial adipose tissue generate inflammatory cytokines and reactive oxygen species (ROS), which induce oxidative stress and contribute to the pathogenesis of CVDs. Nuclear factor erythroid 2-related factor 2 (NRF2; encoded by Nfe2l2 gene) protects against oxidative stress and electrophilic stress. NRF2 participates in the regulation of cell inflammatory responses and lipid metabolism, including the expression of over 1000 genes in the cell under normal and stressed environments. NRF2 is downregulated in diabetes, hypertension, and inflammation. Nfe2l2 knockout mice develop structural and functional cardiac alterations, and NRF2 deficiency in macrophages increases atherosclerosis. Given the endothelial and cardiac protective effects of NRF2 in experimental models, its activation using pharmacological or natural products is a promising therapeutic approach for obesity and CVDs. This review provides a comprehensive summary of the current knowledge on the role of NRF2 in obesity-associated cardiovascular risk factors.

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Angiotensin II requires an intact cardiac thyrotropin-releasing hormone (TRH) system to induce cardiac hypertrophy in mouse

Abstract: requires an intact cardiac thyrotropin-releasing hormone (TRH) system to induce cardiac hypertrophy in mouse. Yjmcc (2018),

Cited by 16 publications

References 13 publications

Cardiomyocyte-targeting exosomes from sulforaphane-treated fibroblasts affords cardioprotection in infarcted rats

Cardiomyocyte-targeting exosomes from sulforaphane-treated fibroblasts affords cardioprotection in infarcted rats

Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure

The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors

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