Cholesterol regulates contractility and inotropic response to β2-adrenoceptor agonist in the mouse atria: Involvement of G i -protein–Akt–NO-pathway

Odnoshivkina, Ulia G.; Sytchev, Vaycheslav I.; Petrov, Alexey M.

doi:10.1016/j.yjmcc.2016.05.001

Cited by 18 publications

(3 citation statements)

References 44 publications

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“…Nevertheless, clinical studies report the β2 adrenoreceptor polymorphism as a risk factor for the development of dyslipidemia 40 . Also high LDL level is able to decrease the β2 adrenoreceptor density in porcine arteria media explants 41 , while cholesterol-depletion promotes β2-adrenerg signaling in mouse atria 42 .…”

Section: Discussionmentioning

confidence: 97%

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

Ágg

Baranyai

Makkos

et al. 2018

Sci Rep

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Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart.

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Section: Discussionmentioning

confidence: 97%

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

Ágg

Baranyai

Makkos

et al. 2018

Sci Rep

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“…On the other hand, FSK has been used to promote the synthesis and production of progesterone; by the way, it leads to increase the uptake of cholesterol by the cells and reducing its levels in serum [ 31 ]. Also, FSK restores cholesterol deposition in human macrophages [ 43 ]. A triangle of three genes was studied to elucidate the normalization effect of FSK on the lipid profile.…”

Section: Discussionmentioning

confidence: 99%

Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation

Abdelazim

Ismail

Abumaghaid

et al. 2021

BioMed Research International

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In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.

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“…However, in our model there was inhibition of these responses indicating it as one of the probable reasons of reduced gestational length. Since most related studies on β-adrenergic signaling in different tissues particularly myocardial tissues have assessed the effect of cholesterol alone under in vitro conditions (Odnoshivkina et al 2017), it is difficult to speculate the effects of triglycerides from these studies. However, isoprenaline (nonselective β-adrenoceptor agonist) response in left ventricular papillary muscle was inhibited in obese Zucker rats compared to lean Zucker rats (Jiang et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Hyperlipidemia impairs uterine β-adrenergic signaling by reducing cAMP in late pregnant rats

et al. 2020

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The aim of the present study was to reveal the effect of hyperlipidemia on β2- and β3-adrenergic signaling in late pregnant rat uterus. Hyperlipidemia was induced in female Wistar rats by feeding a high-fat high-cholesterol diet for 8 weeks before and after mating upto the 21st day of gestation. The effect of hyperlipidemia on β-adrenergic signaling was studied with the help of tension experiments, real-time PCR and cAMP ELISA in 21-day pregnant rat uterus. In tension experiments, hyperlipidemia neither altered the spontaneous contractility nor the oxytocin-induced contractions. However, it decreased the −logEC50 values of β2-adrenoceptor agonist, salbutamol and β3-adrenoceptor agonist, BRL37344. It also decreased the efficacy of adenylyl cyclase activator, forskolin. Further, there was a significant decrease in salbutamol and BRL37344-stimulated cAMP content in uterine tissues. However, there was no alteration in mRNA expressions of β2-adrenoceptor (Adrb2), β3-adrenoceptor (Adrb3) and Gs protein (Gnas) though there was a significant increase in the mRNA expression of Gi protein (Gnai). In conclusion, reduced cAMP content after beta-adrenergic receptor stimulation, which correlates with an increase in Gnai mRNA, may explain the mechanism of the impairment of uterine β-adrenergic signaling in hyperlipidemic pregnant rats. The clinical implication of the present study may relate to reduced myometrial relaxant response to β-adrenergic agonists in high fat-induced uterine dysfunction.

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Cholesterol regulates contractility and inotropic response to β2-adrenoceptor agonist in the mouse atria: Involvement of G i -protein–Akt–NO-pathway

Cited by 18 publications

References 44 publications

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation

Hyperlipidemia impairs uterine β-adrenergic signaling by reducing cAMP in late pregnant rats

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