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Sirtuin 7 mitigates renal ferroptosis, fibrosis and injury in hypertensive mice by facilitating the KLF15/Nrf2 signaling
In conclusion, SIRT7 alleviates renal ferroptosis, lipid peroxidation, and partial EMT under hypertensive status by facilitating the KLF15/Nrf2 signaling, thereby mitigating renal fibrosis, injury and dysfunction. Targeting SIRT7 signaling serves as a promising strategy for hypertension and hypertensive renal injury.PMID:36334846 | DOI:10.1016/j.freeradbiomed.2022.10.320
Source: Free Radical Biology and Medicine - November 5, 2022 Category: Biology Authors: Xue-Ting Li Jia-Wei Song Zhen-Zhou Zhang Mi-Wen Zhang Li-Rong Liang Ran Miao Ying Liu Yi-Hang Chen Xiao-Yan Liu Jiu-Chang Zhong Source Type: research

SIRT1 exerts anti-hypertensive effect via FOXO1 activation in the rostral ventrolateral medulla
Free Radic Biol Med. 2022 Jun 7:S0891-5849(22)00223-4. doi: 10.1016/j.freeradbiomed.2022.06.003. Online ahead of print.ABSTRACTThe rostral ventrolateral medulla (RVLM) is a pivotal region in the central regulation of blood pressure (BP). It has been documented that silent information regulator 2 homolog 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent multifunctional transcription regulatory factor, has many cardiovascular protective effects. However, the role and significance of SIRT1 in the central regulation of cardiovascular activity, especially in RVLM, remains unknown. Therefore, the aim of this study ...
Source: Free Radical Biology and Medicine - June 10, 2022 Category: Biology Authors: Chang-Zhen Ren Zhao-Tang Wu Wen Wang Xing Tan Ya-Hong Yang Yang-Kai Wang Miao-Ling Li Wei-Zhong Wang Source Type: research

Elabela alleviates ferroptosis, myocardial remodeling, fibrosis and heart dysfunction in hypertensive mice by modulating the IL-6/STAT3/GPX4 signaling
In conclusion, elabela antagonizes Ang II-mediated promotion of CMVECs ferroptosis, adverse myocardial remodeling, fibrosis and heart dysfunction through modulating the IL-6/STAT3/GPX4 signaling pathway. Targeting elabela-APJ axis serves as a novel strategy for hypertensive heart diseases.PMID:35122997 | DOI:10.1016/j.freeradbiomed.2022.01.020
Source: Free Radical Biology and Medicine - February 5, 2022 Category: Biology Authors: Zhenzhou Zhang Jianqiong Tang Jiawei Song Mengshi Xie Ying Liu Zhaojie Dong Xiaoyan Liu Xueting Li Miwen Zhang Yihang Chen Hongyu Shi Jiuchang Zhong Source Type: research

Inhibition of RELM-β prevents hypoxia-induced overproliferation of human pulmonary artery smooth muscle cells by reversing PLC-mediated KCNK3 decline
Publication date: Available online 8 February 2020Source: Life SciencesAuthor(s): Linlin Han, Nannan Song, Xiaomin Hu, Afang Zhu, Xin Wei, Jinmin Liu, Shiying Yuan, Weike Mao, Xiangdong ChenAbstractAimsAlthough resistin-like molecule β (RELM-β) is involved in the pathological processes of various lung diseases, such as pulmonary inflammation, asthma and fibrosis, its potential roles in hypoxic pulmonary arterial hypertension (PAH) remain largely unknown. The study aims to investigate whether RELM-β contributes to hypoxia-induced excessive proliferation of human pulmonary artery smooth muscle cells (PASMCs) and to explor...
Source: Life Sciences - February 9, 2020 Category: Biology Source Type: research

LncRNA AK094457 promotes AngII-mediated hypertension and endothelial dysfunction through suppressing of activation of PPARγ
In conclusion, lncRNA AK094457 is identified as a key regulator in blood pressure and endothelial function, which can increase AngII-induced hypertension and endothelial dysfunction via suppression of PPARγ.
Source: Life Sciences - August 14, 2019 Category: Biology Source Type: research

Free heme regulates placenta growth factor through NRF2-antioxidant response signaling.
Abstract Free heme activates erythroblasts to express and secrete Placenta Growth Factor (PlGF), an angiogenic peptide of the VEGF family. High circulating levels of PlGF have been associated in experimental animals and in patients with sickle cell disease with echocardiographic markers of pulmonary hypertension, a life-limiting complication associated with more intense hemolysis. We now show that the mechanism of heme regulation of PlGF requires the contribution of the key antioxidant response regulator NRF2. Mimicking the effect of heme, the NRF2 agonist sulforaphane stimulates the PlGF transcript level nearly 3...
Source: Free Radical Biology and Medicine - August 9, 2019 Category: Biology Authors: Kapetanaki MG, Gbotosho OT, Sharma D, Weidert F, Ofori-Acquah SF, Kato GJ Tags: Free Radic Biol Med Source Type: research

Nox1/Ref-1-mediated activation of CREB promotes Gremlin1-driven endothelial cell proliferation and migration
Publication date: April 2019Source: Redox Biology, Volume 22Author(s): Daniel S. de Jesus, Evan DeVallance, Yao Li, Micol Falabella, Danielle Guimaraes, Sruti Shiva, Brett A. Kaufman, Mark T. Gladwin, Patrick J. PaganoAbstractPulmonary arterial hypertension (PAH) is a complex degenerative disorder marked by aberrant vascular remodeling associated with hyperproliferation and migration of endothelial cells (ECs). Previous reports implicated bone morphogenetic protein antagonist Gremlin 1 in this process; however, little is known of the molecular mechanisms involved. The current study was designed to test whether redox signal...
Source: Redox Biology - February 23, 2019 Category: Biology Source Type: research

Nox1/Ref-1-Mediated Activation of CREB Promotes Gremlin1-Driven Endothelial Cell Proliferation & Migration
Publication date: Available online 8 February 2019Source: Redox BiologyAuthor(s): Daniel S. de Jesus, Evan DeVallance, Yao Li, Micol Falabella, Danielle Guimaraes, Sruti Shiva, Brett Kaufman, Mark T. Gladwin, Patrick J. PaganoAbstractPulmonary arterial hypertension (PAH) is a complex degenerative disorder marked by aberrant vascular remodeling associated with hyperproliferation and migration of endothelial cells (ECs). Previous reports implicated bone morphogenetic protein antagonist Gremlin 1 in this process; however, little is known of the molecular mechanisms involved. The current study was designed to test whether redo...
Source: Redox Biology - February 9, 2019 Category: Biology Source Type: research

HDAC9 is an epigenetic repressor of kidney angiotensinogen establishing a sex difference
ConclusionsThese results indicate that HDAC9 is a novel suppressing factor involved in AGT regulation in PTC, leading to low levels of intrarenal AGT in females. These findings will help to delineate mechanisms underlying sex differences in the development of hypertension and renin-angiotensin system (RAS) associated kidney injury.
Source: Biology of Sex Differences - May 30, 2017 Category: Biology Source Type: research

O-Aminobenzoyl-S-Nitrosoglutathione: a Fluorogenic, Cell Permeable, Pseudo-Substrate for S-Nitrosoglutathione Reductase.
Abstract S-nitrosoglutathione reductase (GSNOR) is a multifunctional enzyme. It can catalyze NADH-dependent reduction of S-nitrosoglutathione (GSNO); as well as NAD(+)-dependent oxidation of hydroxymethylglutathione (HMGSH; an adduct formed by the spontaneous reaction between formaldehyde and glutathione). While initially recognized as the enzyme that is involved in formaldehyde detoxification, increasing amount of research evidence has shown that GSNOR also plays a significant role in nitric oxide mediated signaling through its modulation of protein S-nitrosothiol abundance via transnitrosation reactions with GSN...
Source: Free Radical Biology and Medicine - April 15, 2017 Category: Biology Authors: Sun BL, Palmer L, Alam SR, Adekoya I, Brown-Steinke K, Periasamy A, Mutus B Tags: Free Radic Biol Med Source Type: research

PPARγ depletion stimulates Nox4 expression and human pulmonary artery smooth muscle cell proliferation.
Abstract Hypoxia stimulates pulmonary hypertension (PH) in part by increasing the proliferation of pulmonary vascular wall cells. Recent evidence suggests that signaling events involved in hypoxia-induced cell proliferation include sustained nuclear factor-kappaB (NF-κB) activation, increased NADPH oxidase 4 (Nox4) expression, and downregulation of peroxisome proliferator-activated receptor gamma (PPARγ) levels. To further understand the role of reduced PPARγ levels associated with PH pathobiology, siRNA was employed to reduce PPARγ levels in human pulmonary artery smooth muscle cells (HPASMC) in vitro under n...
Source: Free Radical Biology and Medicine - December 31, 2014 Category: Biology Authors: Bijli KM, Kleinhenz JM, Murphy TC, Kang B, Adesina SE, Sutliff RL, Hart CM Tags: Free Radic Biol Med Source Type: research

Hypoxia downregulates PPARγ via an ERK 1/2-NF-κB-Nox4- dependent mechanism in human pulmonary artery smooth muscle cells.
Abstract The ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), regulates metabolism, cell proliferation, and inflammation. Pulmonary hypertension (PH) is associated with reduced PPARγ expression, and hypoxia exposure regimens that cause PH reduce PPARγ expression. The current study examines mechanisms of hypoxia-induced PPARγ downregulation in vitro and in vivo. Hypoxia reduced PPARγ mRNA and protein levels, PPARγ activity, and the expression of PPARγ-regulated genes in human pulmonary artery smooth muscle cells (HPASMC) exposed to 1% oxygen for 72hours. Simila...
Source: Free Radical Biology and Medicine - May 15, 2013 Category: Biology Authors: Lu X, Bijli KM, Ramirez A, Murphy TC, Kleinhenz J, Michael Hart C Tags: Free Radic Biol Med Source Type: research