Proteome changes in the myocardium of experimental chronic diabetes and hypertension

Ares-Carrasco, Sara; Picatoste, Belén; Camafeita, Emilio; Carrasco-Navarro, S.; Zubiri, Irene; Ortíz, Alberto; Egido, Jesús; López, Juan Antonio; Tuñón, José; Lorenzo, Óscar

doi:10.1016/j.jprot.2011.12.023

Cited by 34 publications

(25 citation statements)

References 50 publications

(118 reference statements)

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“…Findings suggest a role for H3K4me3 of ATP5g3 in proton leak and oxidative stress in the developing heart. Our predicted gene expression results are further supported by proteomics literature, such as ATP synthase protein [56,57] and LIM-binding domain (LBD) protein [57,58] in a similar diabetes-induced rat model, and heat shock proteins (HSPs) in human patients with heart failure [59]. …”

Section: Discussionsupporting

confidence: 75%

Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

et al. 2017

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Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0.1). In the HF-diet exposed offspring, 54% of the annotated genes showed the gene-activating mark trimethylated lysine 4. Many of these genes (1) are associated with the “metabolic process” in general and particularly with “positive regulation of cholesterol biosynthesis” (FDR = 0.03); (2) overlap with 455 quantitative trait loci for blood pressure, body weight, serum cholesterol (all, FDR < 0.1); and (3) are linked to cardiac disease susceptibility/progression, based on disease ontology analyses and scientific literature. These results indicate that maternal HF-diet changes the cardiac histone signature in offspring suggesting a fuel-mediated epigenetic reprogramming of cardiac tissue in utero.

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Section: Discussionsupporting

confidence: 75%

Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

et al. 2017

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“…This may explain the lack of beating activity of the resulting cardiomyocytes. In addition, even with a significantly increased gene expression related to cell contraction (Myl2 and Tnnt) 29,30 on FDM, it seems that current upregulation of such genes is insufficient to prove functional contractility of differentiated H9c2. Information about Myl2 protein expression that is lacked in this study might give a better insight, along with cTnT expression as shown in Figure 3.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyoblast (H9c2) Differentiation on Tunable Extracellular Matrix Microenvironment

Suhaeri

Subbiah

Van

et al. 2015

Tissue Engineering Part A

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Extracellular matrices (ECM) obtained from in vitro-cultured cells have been given much attention, but its application in cardiac tissue engineering is still limited. This study investigates cardiomyogenic potential of fibroblast-derived matrix (FDM) as a novel ECM platform over gelatin or fibronectin, in generating cardiac cell lineages derived from H9c2 cardiomyoblasts. As characterized through SEM and AFM, FDM exhibits unique surface texture and biomechanical property. Immunofluorescence also found fibronectin, collagen, and laminin in the FDM. Cells on FDM showed a more circular shape and slightly less proliferation in a growth medium. After being cultured in a differentiation medium for 7 days, H9c2 cells on FDM differentiated into cardiomyocytes, as identified by stronger positive markers, such as a-actinin and cTnT, along with more elevated gene expression of Myl2 and Tnnt compared to the cells on gelatin and fibronectin. The gap junction protein connexin 43 was also significantly upregulated for the cells differentiated on FDM. A successive work enabled matrix stiffness tunable; FDM crosslinked by 2wt% genipin increased the stiffness up to 8.5 kPa, 100 times harder than that of natural FDM. The gene expression of integrin subunit a5 was significantly more upregulated on FDM than on crosslinked FDM (X-FDM), whereas no difference was observed for b1 expression. Interestingly, X-FDM showed a much greater effect on the cardiomyoblast differentiation into cardiomyocytes over natural one. This study strongly indicates that FDM can be a favorable ECM microenvironment for cardiomyogenesis of H9c2 and that tunable mechanical compliance induced by crosslinking further provides a valuable insight into the role of matrix stiffness on cardiomyogenesis.

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“…Long-term hyperglycemia promotes negative effects on the heart, affecting the cardiac expression of lipid-, glucose- and ketone bodies-metabolic, signalling and stress-response genes [30,31]. Chronic hyperglycemia is related with cardiac fibrosis, coronary disease and increased risk of heart attack, and it has been also associated with higher levels of toxic glycolytic intermediates and troponin-T, a blood marker for heart damage [32].…”

Section: Discussionmentioning

confidence: 99%

Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes

Ramírez

Klett-Mingo

Ares-Carrasco

et al. 2013

Cardiovasc Diabetol

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BackgroundCardiac steatosis and apoptosis are key processes in diabetic cardiomyopathy, but the underlying mechanisms have not been elucidated, leading to a lack of effective therapy. The mineralocorticoid receptor blocker, eplerenone, has demonstrated anti-fibrotic actions in the diabetic heart. However, its effects on the fatty-acid accumulation and apoptotic responses have not been revealed.MethodsNon-hypertensive Zucker Diabetic Fatty (ZDF) rats received eplerenone (25 mg/kg) or vehicle. Zucker Lean (ZL) rats were used as control (n = 10, each group). After 16 weeks, cardiac structure and function was examined, and plasma and hearts were isolated for biochemical and histological approaches. Cultured cardiomyocytes were used for in vitro assays to determine the direct effects of eplerenone on high fatty acid and high glucose exposed cells.ResultsIn contrast to ZL, ZDF rats exhibited hyperglycemia, hyperlipidemia, insulin-resistance, cardiac steatosis and diastolic dysfunction. The ZDF myocardium also showed increased mitochondrial oxidation and apoptosis. Importantly, eplerenone mitigated these events without altering hyperglycemia. In cultured cardiomyocytes, high-concentrations of palmitate stimulated the fatty-acid uptake (in detriment of glucose assimilation), accumulation of lipid metabolites, mitochondrial dysfunction, and apoptosis. Interestingly, fatty-acid uptake, ceramides formation and apoptosis were also significantly ameliorated by eplerenone.ConclusionsBy blocking mineralocorticoid receptors, eplerenone may attenuate cardiac steatosis and apoptosis, and subsequent remodelling and diastolic dysfunction in obese/type-II diabetic rats.

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Proteome changes in the myocardium of experimental chronic diabetes and hypertension

Cited by 34 publications

References 50 publications

Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

Cardiomyoblast (H9c2) Differentiation on Tunable Extracellular Matrix Microenvironment

Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes

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