Vitamin A for the heart: progress for cardiac hypertrophy regression?

Maier, Lars S.

doi:10.1152/ajpheart.00002.2008

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…This role for RBP4 is supported by the reduced cardiac hypertrophy in our RBP4-KO mice. Retinoids have been shown to protect against cardiac hypertrophy (36), but retinol and RE levels were similar in the hearts of the WT and RBP4-KO mice in our study and therefore do not explain the differences in hypertrophy in our model. Likewise, the differences cannot be explained by alterations in local RBP4 expression, as we did not detect any cardiac RBP4 protein in lean or obese mice (data not shown).…”

Section: Discussioncontrasting

confidence: 71%

Novel role for retinol-binding protein 4 in the regulation of blood pressure

et al. 2015

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Elevated levels of serum retinol-binding protein 4 (RBP4) contribute to insulin resistance and correlate with increased prevalence of hypertension and myocardial infarction. We sought to determine whether lowering RBP4 would improve blood pressure (BP) and protect against obesity-or angiotensin (Ang)-II-induced hypertension. Systolic and diastolic BP were lower in the RBP4-knockout (RBP4-KO) mice and higher in the RBP4-overexpressing (RBP4-Tg) mice compared with BP in the wild-type (WT) littermates. Carbachol-induced vasodilatation was increased in arteries from the RBP4-KO compared with the WT mice and was impaired in the RBP4-Tg mice. Aortic eNOS Ser1177 phosphorylation was enhanced ∼50% in the RBP4-KO mice, with no change in total eNOS protein. Feeding a high-fat diet increased BP in the RBP4-KO mice only to the level in the WT mice fed chow and had no effect on aortic eNOS Ser1177 phosphorylation. Ang-II infusion resulted in 22 mmHg lower systolic BP in the RBP4-KO than in the WT mice, although the relative BP increase over saline infusion was ∼30% in both. Ang-II treatment decreased aortic eNOS Ser1177 phosphorylation in the WT and RBP4-KO mice, but phosphorylation remained higher in the RBP4-KO mice. Cardiac hypertrophy with Ang-II treatment was diminished by 56% in the RBP4-KO mice. Thus, elevated serum RBP4 raises BP and lack of RBP4 reduces it, with commensurate changes in aortic eNOS Ser1177 phosphorylation. Lowering RBP4 may reduce BP through enhanced eNOS-mediated vasodilatation and may be a novel therapeutic approach for hypertension.-Kraus, B. J., Sartoretto, J. L., Polak, P., Hosooka, T., Shiroto, T., Eskurza, I., Lee, S.-A., Jiang, H., Michel, T., Kahn, B. B. Novel role for retinol-binding protein 4 in the regulation of blood pressure. FASEB J. 29, 3133-3140 (2015). www.fasebj.org

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Section: Discussioncontrasting

confidence: 71%

Novel role for retinol-binding protein 4 in the regulation of blood pressure

et al. 2015

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“…Vitamin A and its subsequent metabolism into retinoic acid have been proposed as a potential means for the regression of cardiac hypertrophy (Maier 2008). The atRA treatment prevents medial thickening of intrarenal and intramyocardial arteries in the SHR model (Lu et al 2003), a model known to have up-regulated AT1 expression.…”

Section: Discussionmentioning

confidence: 99%

13-cis-Retinoic acid specific down-regulation of angiotensin type 1 receptor in rat liver epithelial and aortic smooth muscle cells

Snyder

Thekkumkara²

2011

Journal of Molecular Endocrinology

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Transcriptional repression through cis-and trans-acting factors enabling an alternate approach to control angiotensin type 1 receptor (AT1 or AGTR1 as listed in the MGI database) expression has not been studied. In previous investigations, treatment with retinoic acid was found to be associated with enhanced insulin sensitivity. In our previous study, expression of AT1 was found to be inversely correlated with intracellular glucose concentrations. Therefore, we hypothesized that 13-cis-retinoic acid (13cRA), an antioxidant, enhances insulin-sensitive glucose-mediated downregulation of the AT1. In this study, we used continuously passaged rat liver epithelial cells. Our study shows that cells exposed to 13cRA specifically down-regulated the AT1 protein in a dose-and time-dependent manner, independently of any change in receptor affinity. Down-regulation of the AT1 expression leads to reduced AngII-mediated intracellular calcium release, a hallmark of receptor-mediated intracellular signaling. Similarly with receptor down-regulation, we observed a significant reduction in AT1 mRNA; however, the AT1 down-regulation was independent of insulin-sensitive glucose uptake and retinoic acid receptor activation (RAR/RXR). Treatment with 13cRA resulted in phosphorylation of p42/p44 MAP kinases in these cells. Subsequent studies using MEK inhibitor PD98059 prevented 13cRA-mediated AT1 down-regulation and restored AngII-mediated intracellular calcium response. Furthermore, 13cRA-mediated inhibitory effects on AT1 were validated in primary rat aortic smooth muscle cells. In summary, our results demonstrate for the first time that 13cRA has a glucose-and RAR/RXR-independent mechanism for transcriptional inhibition of AT1, suggesting its therapeutic potential in systems in which AT1 expression is deregulated in insulin-sensitive and -insensitive tissues.

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“…6 Studies have demonstrated that an enzyme that inactivates MAPK, namely mitogen-activated protein kinase phosphatase 1 (MKP-1), is induced by retinoids at the transcriptional level and that the induced MKP-1 plays a significant role in mediating both MAPK inhibition and the antiapoptotic effect of atRA on oxidative stress. 7,8 Recently, 3-hydroxy-3-methylglutaryl-coenzyme-A (HMGCoA) reductase inhibitors, also called statins, were reported to inhibit Ang II-induced phosphorylation of MAPK. Blockade of the HMGCoA reductase by statins disrupts the mevalonate pathway.…”

Section: Introductionmentioning

confidence: 99%