Correction: Simvastatin Attenuates Oxidative Stress, NF-κB Activation, and Artery Calcification in LDLR-/- Mice Fed with High Fat Diet via Down-regulation of Tumor Necrosis Factor-α and TNF Receptor 1

Lin, Chih-Pei; Huang, Po‐Hsun; Lai, Chung Fang; Chen, Jaw-Wen; Lin, Shing‐Jong; Chen, Jia-Shiong

doi:10.1371/journal.pone.0148590

Cited by 4 publications

(14 citation statements)

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“…Aorta samples were cut into 4 sections and processed for histological staining as described in our previous study [30]. Para n sections (5 µm) from the dissenting aorta were stained using various agents for semi-quanti cation of atherosclerotic lesion size and severity (hematoxylin and eosin (H&E) staining) and aortic calcium deposition (alizarin red S staining).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…catalog number C0075C). The cells were grown and passaged as described previously [30]. Brie y, the HASMCs were grown in M231 medium containing SMC growth supplement and a 1% antibiotic-antimycotic mixture in an atmosphere of 95% air and 5% CO 2 at 37°C in plastic asks.…”

Section: Cell Cultures and Cell Viability Assaymentioning

confidence: 99%

“…The aortic segments from experimental mice were extracted using 0.6 N HCl for 24 h and the calcium content of the extracts were determined using a BioChain Calcium Kit (BioChain, Hayward, CA, USA) as previously described [30]. The results were expressed as µg/mg of wet aortic tissues.…”

Section: Quanti Cation Of Aorta or Cultured Hasmc Calcium Depositmentioning

confidence: 99%

“…Nuclear pellets were resuspended in 70 µl ice-cold buffer C (20 mM HEPES/NaOH, pH 7.9; 1.5 mM MgCl 2 ; 1 mM DTT; 0.2 mM EDTA; 420 mM NaCl; 25% glycerol; 0.5 mM PMSF; 2 µg/mL aprotinin; 2 µg/ mL pepstatin; 2 µg/mL leupeptin), incubated on ice for 30 min with intermittent mixing, and then centrifuged at 15,000 ⋅ g for 30 min at 4°C. Cell membrane fractions were prepared as described previously [30] with some modi cations. Brie y, HASMCs were lysed in a lysis buffer (10 mM Tris-HCl, 1 mM EDTA, 1 mM PMSF, 10 µg/mL aprotinin, and 0.5 µg/mL leupeptin; pH 7.5).…”

Section: Extraction Of Cellular Proteinsmentioning

confidence: 99%

“…It was reported that TNF-α play a crucial role in artery calci cation in diabetes LDLR −/− mice [7]. Our previously study showed that tumor necrosis factor (TNF-α) and vascular TNF receptor (TNFR) signaling lead to human artery smooth muscle cell (HASMC) calci cation and antioxidants blunt the TNF-α/TNFR signaling to retard the HASMC calci cation [30]. We hypothesized that the hyperglycemia and hyperlipidemia of the DM2 patients induce systematic oxidative and the resultant elevation of circulatory (TNF)-α and S100A2 triggers the vascular calci cation.…”

Section: Introductionmentioning

confidence: 99%

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Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Attenuates Arterial Calcification By Downregulating Oxidative Stress-Induced Receptor for Advanced Glycation End Products in Low-Density Lipoprotein Receptor Knockout Mice

Lin¹,

Huang²,

Chen³

et al. 2021

Preprint

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Background: Plasma advanced glycation end products (AGEs) activates the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus patient vascular complications. Attenuating the activation of RAGE may exert a protective effect against the development of cardiovascular disease. Dipeptidyl peptidase-4 (DPP4) inhibitors are a new class of oral hypoglycemic agents for the treatment of type 2 diabetes mellitus. Whether sitagliptin, a DPP-4 inhibitor, has a beneficial effect on vascular calcification remains undetermined. Methods: In the present study, we fed low-density lipoprotein receptor knockout (LDLR-/-) mice a high fat diet to induce diabetic mellitus and studied the effect of orally administered sitagliptin on the high fat diet fed LDLR-/- mice aorta medial calcification, RAGE expression, oxidative stress, aorta calcium content. Tumor necrosis factor (TNF)-α combined with S100A12 was used to induce HASMC oxidative stress, activation of NADPH, up-regulation of the bone markers and RAGE expression, and cell calcium deposition. Effect of sitagliptin, siRNA for RAGE and apocynin on blunting TNF-α and S100A12 induced HASMC oxidative stress, calcification and NADPH activation were also investigated. Results: Sitagliptin attenuated the HFD-induced LDLR-/- mice hyperlipidemia, hyperglycemia, increase in serum TNF-α, aorta calcium deposition and the expression of RAGE in the medial layer of the aorta. TNF-α combined with S100A12 stimulated HASMC RAGE expression, calcium deposition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activation, and up-regulation of bone marker (bone morphogenetic protein-2, Msh homeobox 2, and runt‑related transcription factor 2) expression. Sitagliptin and apocynin (APO), an NADPH oxidase inhibitor, suppressed the TNF-α+S100A12 treatment effects on the activation of NADPH oxidase and Nuclear factor (NF)-κB and the resultant oxidative stress, up-regulation of RAGE and bone markers expression and calcium deposition. Our findings suggest that sitagliptin imparts its protective effect by suppressing NADPH oxidase and NF-κB activation to blunt the up-regulation of RAGE expression.Conclusion: Our findings suggest that sitagliptin may suppress the initiation and progression of artery calcification by inhibiting the activation of NADPH oxidase and NF-κB and the resultant up-regulation of expression of RAGE.

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Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Section: Cell Cultures and Cell Viability Assaymentioning

confidence: 99%

Section: Quanti Cation Of Aorta or Cultured Hasmc Calcium Depositmentioning

confidence: 99%

Section: Extraction Of Cellular Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Attenuates Arterial Calcification By Downregulating Oxidative Stress-Induced Receptor for Advanced Glycation End Products in Low-Density Lipoprotein Receptor Knockout Mice

Lin¹,

Huang²,

Chen³

et al. 2021

Preprint

Self Cite

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show abstract

Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice

Lin

Huang

Chen

et al. 2021

Sci Rep

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Diabetes is a complex disease characterized by hyperglycemia, dyslipidemia, and insulin resistance. Plasma advanced glycation end products (AGEs) activated the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus (T2DM) patient vascular complications. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, is a new oral hypoglycemic agent for the treatment of T2DM. However, the beneficial effects on vascular calcification remain unclear. In this study, we used a high-fat diet (HFD)-fed low-density lipoprotein receptor deficiency (LDLR−/−) mice model to investigate the potential effects of sitagliptin on HFD-induced arterial calcification. Mice were randomly divided into 3 groups: (1) normal diet group, (2) HFD group and (3) HFD + sitagliptin group. After 24 weeks treatment, we collected the blood for chemistry parameters and DPP4 activity measurement, and harvested the aorta to evaluate calcification using immunohistochemistry and calcium content. To determine the effects of sitagliptin, tumor necrosis factor (TNF)-α combined with S100A12 was used to induce oxidative stress, activation of nicotinamide adenine dinucleotide phosphate (NADPH), up-regulation of bone markers and RAGE expression, and cell calcium deposition on human aortic smooth muscle cells (HASMCs). We found that sitagliptin effectively blunted the HFD-induced artery calcification and significantly lowered the levels of fasting serum glucose, triglyceride (TG), nitrotyrosine and TNF-α, decreased the calcium deposits, and reduced arterial calcification. In an in-vitro study, both S100A12 and TNF-α stimulated RAGE expression and cellular calcium deposits in HASMCs. The potency of S100A12 on HASMCs was amplified by the presence of TNF-α. Sitagliptin and Apocynin (APO), an NADPH oxidase inhibitor, inhibited the TNF-α + S100A12-induced NADPH oxidase and nuclear factor (NF)-κB activation, cellular oxidative stress, RAGE expression, osteo transcription factors expression and calcium deposition. In addition, treatment with sitagliptin, knockdown of RAGE or TNF-α receptor blunted the TNF-α + S100A12-induced RAGE expression. Our findings suggest that sitagliptin may suppress the initiation and progression of arterial calcification by inhibiting the activation of NADPH oxidase and NF-κB, followed by decreasing the expression of RAGE.

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Arterial Stiffness

Chen

Zhao

2020

ATVB

119

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This review focuses on the association between vascular calcification and arterial stiffness, highlighting the important genetic factors, systemic and local microenvironmental signals, and underlying signaling pathways and molecular regulators of vascular calcification. Elevated oxidative stress appears to be a common procalcification factor that induces osteogenic differentiation and calcification of vascular cells in a variety of disease conditions such as atherosclerosis, diabetes mellitus, and chronic kidney disease. Thus, the role of oxidative stress and oxidative stress–regulated signals in vascular smooth muscle cells and their contributions to vascular calcification are highlighted. In relation to diabetes mellitus, the regulation of both hyperglycemia and increased protein glycosylation, by AGEs (advanced glycation end products) and O -linked β-N-acetylglucosamine modification, and its role in enhancing intracellular pathophysiological signaling that promotes osteogenic differentiation and calcification of vascular smooth muscle cells are discussed. In the context of chronic kidney disease, this review details the role of calcium and phosphate homeostasis, parathyroid hormone, and specific calcification inhibitors in regulating vascular calcification. In addition, the impact of the systemic and microenvironmental factors on respective intrinsic signaling pathways that promote osteogenic differentiation and calcification of vascular smooth muscle cells and osteoblasts are compared and contrasted, aiming to dissect the commonalities and distinctions that underlie the paradoxical vascular-bone mineralization disorders in aging and diseases.

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Correction: Simvastatin Attenuates Oxidative Stress, NF-κB Activation, and Artery Calcification in LDLR-/- Mice Fed with High Fat Diet via Down-regulation of Tumor Necrosis Factor-α and TNF Receptor 1

Cited by 4 publications

References 1 publication

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Attenuates Arterial Calcification By Downregulating Oxidative Stress-Induced Receptor for Advanced Glycation End Products in Low-Density Lipoprotein Receptor Knockout Mice

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Attenuates Arterial Calcification By Downregulating Oxidative Stress-Induced Receptor for Advanced Glycation End Products in Low-Density Lipoprotein Receptor Knockout Mice

Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice

Arterial Stiffness

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