Endothelin-1-Induced Cell Hypertrophy in Cardiomyocytes is Improved by Fenofibrate: Possible Roles of Adiponectin

Jen, Hsu Lung; Yin, Wei Hsian; Chen, Jaw Wen; Lin, Shing Jong

doi:10.5551/jat.36368

Cited by 15 publications

(10 citation statements)

References 37 publications

(51 reference statements)

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“…Treatment with fenofibrate improved LV function under these conditions. These findings are in agreement with a previous study that demonstrated that fenofibrate attenuated daunorubicin-induced cardiac toxicity 27 . Daunorubicin and doxorubicin show some differences in their clinically approved indications, especially the use of doxorubicin to treat solid tumors 34 .…”

Section: Discussionsupporting

confidence: 94%

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Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway

Huang

Yin

Chen

et al. 2021

Sci Rep

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Endothelial progenitor cells (EPCs) improve endothelial impairment, which in turn restores endothelial function in patients with heart failure (HF). In the present study, we tested whether fenofibrate, with its anti-inflammatory and vasoprotective effects, could improve myocardial function by activating EPCs through the eNOS pathway in a doxorubicin (DOX)-induced cardiomyopathy mouse model. Wild-type mice were divided into 4 groups and treated with vehicle, DOX + saline, DOX + fenofibrate, and DOX + fenofibrate + L-NAME (N(ω)-nitro-L-arginine methyl ester). DOX-induced cardiac atrophy, myocardial dysfunction, the number of circulating EPCs and tissue inflammation were analyzed. Mice in the DOX + fenofibrate group had more circulating EPCs than those in the DOX + saline group (2% versus 0.5% of total events, respectively) after 4 weeks of treatment with fenofibrate. In addition, the inhibition of eNOS by L-NAME in vivo further abolished the fenofibrate-induced suppression of DOX-induced cardiotoxic effects. Protein assays revealed that, after DOX treatment, the differential expression of MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) between saline- and DOX-treated mice was involved in the progression of HF. Mechanistically, fenofibrate promotes Akt/eNOS and VEGF (vascular endothelial growth factor), which results in the activation of EPC pathways, thereby ameliorating DOX-induced cardiac toxicity.

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Section: Discussionsupporting

confidence: 94%

“…First part as Fig. 1 A were administered group1) saline, 2) fenofibrate (Santa Cruz Biotechnology, Santa Cruz, CA, USA) orally in feed for 4 weeks (20 mg kg-1 d-1), 3) fenofibrate orally in feed for 4 weeks 100 mg kg −1 d −1 26 , 27 . Second part as Fig.…”

Section: Methodsmentioning

confidence: 99%

Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway

Huang

Yin

Chen

et al. 2021

Sci Rep

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“…Stimulation by ET-1 has been shown to induce cardiac hypertrophy both in vitro (Jen et al, 2017) and in vivo (Archer et al, 2017). High levels of plasma big endothelin-1, the biological precursor of endothelin-1, were observed to predict a worse prognosis for patients with hypertrophic cardiomyopathy (Wang et al, 2017b).…”

Section: Potential Circulating Biomarkers During Cardiac Hypertrophymentioning

confidence: 99%

Endothelial cell modulation of cardiomyocyte gene expression

Jiang

Mohr

Ullrich

et al. 2019

Experimental Cell Research

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WB Western blot WGA Wheat germ agglutinin β-MHC -Myosin heavy chain 2013, Fredriksen et al., 2001). Kidney disease is commonly found in heart failure (HF) patients (Grande et al., 2017). It was found that GFR is associated with the degree of cardiac diastolic dysfunction and adverse clinical outcomes (Jain et al., 2017). A recent nationwide population-based cohort study showed that heart failure patients have a higher risk of developing dementia (Adelborg et al., 2017). Studies also revealed post-mortem that 73.6% ± 7.0% of all cardiomyocytes were mono-nucleated, 25.5% ± 7.4% were bi-nucleated, and 1.0% ± 1.2% were tri-nucleated in the heart of individuals aged one month to 73 years. In agreement with previous studies (Mollova et al., 2013, Olivetti et al., 1996), they established that already 1 month after birth; the final number of cardiomyocytes was reached (3.2 ± 0.75 × 10 9 cells) and remained constant throughout life. By stereological measuring the average volume of cardiomyocytes at different ages, it was found that the adaptive about 3-fold greater (endothelium-derived contracting factors) (Flammer et al., 2012). Furchgott and Zawadzki (Furchgott and Zawadzki, 1980) first described the phenomenon of endothelium-dependent relaxation in 1980. Subsequently, the identification of nitric oxide (NO) as the crucial endothelium-derived mediator of vascular relaxation led to substantial progress in cardiovascular research (Flammer et al., 2012). In addition to with arterial hypertension and echocardiographically documented left ventricular hypertrophy, who received either the AT 1 receptor blocker losartan or the β 1 receptor blocker atenolol, were much less likely to experience such a major cardiovascular event (Kjeldsen et al., 2002). Also whereby NT-proBNP levels are more sensitive and specific to distinguish HF from non-HF subjects (Fonseca et al., 2004). NT-proBNP levels were also suggested to be highly predictive of incident atrial fibrillation, the most common cardiac rhythm abnormality, after adjustment for an extensive number of covariates (Patton et al., 2009). Although ANP and BNP have been recommended to provide prognostic information

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“…Numerous approaches have been developed to address the various facets of stem cell-derived cardiomyocyte immaturity including, but not limited to, engineered 3D hPSC-derived cardiomyocyte tissue constructs (Mills et al, 2017a;Voges et al, 2017), mechanical loading (Leonard et al, 2018;Ovchinnikova et al, 2018), pulsatile flow (Shen et al, 2017), electrical pacing (Ronaldson-Bouchard et al, 2018), and nanopatterning culture surfaces (Carson et al, 2016) in addition to adaptions to media composition (e.g., supplementation with thyroid hormone (Yang et al, 2014b) or endothelin-1 (Drawnel et al, 2013;Jen et al, 2017)) and the available metabolic substrate (Mills et al, 2017a;Yang et al, 2019). These approaches exert unique and synergistic effects on hPSC-derived cardiomyocytes and can be combined depending on the experimental endpoint and study objectives.…”

Section: Improved Approaches To Model the Heart In Vitromentioning

confidence: 99%

“…For example, endothelin-1 is a factor released primarily by endothelium that drives cardiomyocyte hypertrophy among other functions in development (Dhaun and Webb, 2019;Drawnel et al, 2013). Endothelin-1 has been used to supplement media to induce cardiomyocyte growth and model cardiac hypertrophy in vitro (Jen et al, 2017). Additionally, thyroid hormone signalling increases after birth and has been shown to improve cardiomyocyte maturation in vivo (Hirose et al, 2019;Marshall et al, 2019) and in vitro (Ribeiro et al, 2015;van den Berg et al, 2015;Yang et al, 2014b).…”

Section: Improved Approaches To Model the Heart In Vitromentioning

confidence: 99%

Genetic regulation of cardiac differentiation at single-cell resolution

Friedman¹

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Endothelin-1-Induced Cell Hypertrophy in Cardiomyocytes is Improved by Fenofibrate: Possible Roles of Adiponectin

Cited by 15 publications

References 37 publications

Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway

Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway

Endothelial cell modulation of cardiomyocyte gene expression

Genetic regulation of cardiac differentiation at single-cell resolution

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