The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice

Greig, Fiona H.; Ewart, Marie-Ann; McNaughton, E.; Cooney, Josephine; Spickett, Corinne M.; Kennedy, Simon

doi:10.1016/j.vph.2015.07.010

Cited by 8 publications

(9 citation statements)

References 49 publications

(66 reference statements)

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“…3a ). A similar attenuation caused by fat-feeding on aortic relaxation to other vasodilators such as the AMPK activating agent A769662 has also been observed by us previously [ 19 ]. Relaxation to A769662 was partly dependent on IP3R activation since it was significantly attenuated by the very selective IP3R antagonist xestospongin C (5 µ M ) in C57 mice (Fig.…”

Section: Resultssupporting

confidence: 85%

Changes in IP3 Receptor Expression and Function in Aortic Smooth Muscle of Atherosclerotic Mice

et al. 2017

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Peroxynitrite is an endothelium-independent vasodilator that induces relaxation via membrane hyperpolarization. The activation of IP3 receptors triggers the opening of potassium channels and hyperpolarization. Previously we found that relaxation to peroxynitrite was maintained during the development of atherosclerosis due to changes in the expression of calcium-regulatory proteins. In this study we investigated: (1) the mechanism of peroxynitrite-induced relaxation in the mouse aorta, (2) the effect of atherosclerosis on relaxation to peroxynitrite and other vasodilators, and (3) the effect of atherosclerosis on the expression and function of the IP3 receptor. Aortic function was studied using wire myography, and atherosclerosis was induced by fat-feeding ApoE^-/- mice. The expression of IP3 receptors was studied using Western blotting and immunohistochemistry. Relaxation to peroxynitrite was attenuated by the IP3 antagonists 2-APB and xestospongin C and also the K_v channel blocker 4-aminopyridine (4-AP). Atherosclerosis attenuated vasodilation to cromakalim and the AMPK activator A769662 but not peroxynitrite. Relaxation was attenuated to a greater extent by 2-APB in atherosclerotic aortae despite the reduced expression of IP3 receptors. 4-AP was less effective in ApoE^-/- mice fat-fed for 4 months. Peroxynitrite relaxation involves an IP3-induced calcium release and K_V channel activation. This mechanism becomes less important as atherosclerosis develops, and relaxation to peroxynitrite may be maintained by increased calcium extrusion.

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Section: Resultssupporting

confidence: 85%

Changes in IP3 Receptor Expression and Function in Aortic Smooth Muscle of Atherosclerotic Mice

et al. 2017

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“…Furthermore, AMPK plays an important role in the immunoreaction-mediated progression of atherosclerosis and is expressed in vascular endothelial cells, where it maintains endothelial homeostasis in response to various proinflammatory factors [14,15]. AMPK activation by AICAR (5-aminoimidazole-4-carboximide ribonucleotide) suppresses tumor necrosis factor-α (TNFα)/nuclear factor-κB (NFκB) in vascular endothelial cells [16,17] and also attenuates atherosclerosis by downsizing atherosclerotic lesions in ApoE (apolipoprotein E)-null mice [18,19]. However, the effects of BAIBA on cardiovascular disease remain unclear, although BAIBA has been demonstrated to have antiinflammatory properties [8,10].…”

Section: Introductionmentioning

confidence: 99%

BAIBA Attenuates the Expression of Inflammatory Cytokines and Attachment Molecules and ER Stress in HUVECs and THP-1 Cells

Lee¹,

Yun²,

Choi³

et al. 2018

Pathobiology

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Objective: β-Aminoisobutyric acid (BAIBA), a myokine, is a thymine catabolite that is induced during exercise, leading to browning of white fat, hepatic fatty acid oxidation, and suppression of hepatic lipogenesis. However, the effects of BAIBA on the progression of atherosclerosis remain unclear. Methods: We performed a Western blot analyses to determine various protein expression. ELISAs (enzyme-linked immunosorbent assays), cell adhesion assays, and cell viability assays were also performed on human umbilical vascular endothelial cells (HUVECs) and human monocytes (THP-1 cells). Results: In the current study, we demonstrate that BAIBA suppresses atherosclerotic reactions caused by lipopolysaccharide (LPS) treatment via an AMPK-dependent pathway. Treatment of HUVECs and THP-1 cells with BAIBA inhibited the LPS-induced phosphorylation of nuclear factor-κB (NFκB) and the secretion of proinflammatory cytokines. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly decreased after BAIBA treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell toxicity were significantly decreased after BAIBA treatment of HUVECs. Notably, all of these proatherosclerotic effects were fully abrogated by treatment with small interfering RNA targeting AMPK. Conclusion: BAIBA ameliorates LPS-induced atherosclerotic reactions via AMPK-mediated suppression of inflammation and ER stress.

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“…In addition to modulating lipogenesis and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis [15,18], both recent studies [19,20] and our studies [21,22] have revealed that AMPK can also regulate oxidative stress through NF-E2 related factor (Nrf2)-mediated phase II antioxidant enzymes. Evidence has also suggested a correlation between hyperlipidemia and the AMPK pathway in the vascular system [23,24]. We observed obese mice or rats with hyperlipidemia exhibit decreased AMPK activity accompanied by mitochondrial dysfunction and oxidative stress in various organs [22,25,26].…”

Section: Introductionmentioning

confidence: 55%

“…AMPK is a well-known energy sensor and metabolic regulator that promotes catabolic pathways such as fatty acid oxidation and inhibits anabolic pathways such as lipogenesis. Although recent investigation has suggested a possible link between hyperlipidemia and the AMPK pathway in the vascular system [23,24], the regulatory role of AMPK in hyperlipidemia-induced impairment in other tissues, except for the vascular system, remains largely unclear. In our current research, we discovered a deficiency in AMPK activity in both the liver and heart after P407 treatment, and HAE treatment restored AMPK activity in both of these tissues ( Figure 3A-F).…”

Section: Discussionmentioning

confidence: 99%

“…Tissue homogenate and serum samples were obtained according to the previous method [23]. Reduced glutathione (GSH), oxydized glutathione (GSSG), triglyceride (TG), and total cholesterol (TC) contents as well as glutathione S-transferase (GST), glutathione peroxidase (GPX), γ-glutamylcysteine synthetase (γ-GCS), and total superoxide dismutase (SOD) activities were analyzed by using detection kits (Jiancheng, Nanjing, China).…”

Section: Biochemical Analysismentioning

confidence: 99%

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Herba houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade

Cao

Liu

et al. 2020

Nutrients

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Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

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The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice

Cited by 8 publications

References 49 publications

Changes in IP3 Receptor Expression and Function in Aortic Smooth Muscle of Atherosclerotic Mice

Changes in IP3 Receptor Expression and Function in Aortic Smooth Muscle of Atherosclerotic Mice

BAIBA Attenuates the Expression of Inflammatory Cytokines and Attachment Molecules and ER Stress in HUVECs and THP-1 Cells

Herba houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade

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