SOD2 ameliorates pulmonary hypertension in a murine model of sleep apnea via suppressing expression of NLRP3 in CD11b+ cells

Fu, Cuiping; Hao, Shengyu; Liu, Zilong; Xie, Liang; Wu, Xu; Wu, Xiaodan; Li, Shanqun

doi:10.1186/s12931-019-1270-0

Cited by 12 publications

(10 citation statements)

References 41 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 78 , 79 Additionally, SOD2 deficiency is emerging as a crucial focus of research in PAH and is demonstrated to be involved in the phenotypic switching of cells. 75 , 80 , 81 Altogether, the NFU1 model resonates these findings and brings SOD2 and ROS to the intersection of mitochondrial dysfunction and phenotypic switching of the PASMC. Confirming the role of mROS in proliferation, we show that the NFU1 cells have attenuated proliferation rates when the mROS is quenched using the mitochondrial-targeted antioxidant MT.…”

Section: Discussionmentioning

confidence: 56%

Single Mutation in the NFU1 Gene Metabolically Reprograms Pulmonary Artery Smooth Muscle Cells

James

Zemskova

Eccles

et al. 2021

ATVB

View full text Add to dashboard Cite

Objective: NFU1 is a mitochondrial iron-sulfur scaffold protein, involved in iron-sulfur assembly and transfer to complex II and LAS (lipoic acid synthase). Patients with the point mutation NFU1 G208C and CRISPR/CAS9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9)-generated rats develop mitochondrial dysfunction leading to pulmonary arterial hypertension. However, the mechanistic understanding of pulmonary vascular proliferation due to a single mutation in NFU1 remains unresolved. Approach and Results: Quantitative proteomics of isolated mitochondria showed the entire phenotypic transformation of NFU1 G206C rats with a disturbed mitochondrial proteomic landscape, involving significant changes in the expression of 208 mitochondrial proteins. The NFU1 mutation deranged the expression pattern of electron transport proteins, resulting in a significant decrease in mitochondrial respiration. Reduced reliance on mitochondrial respiration amplified glycolysis in pulmonary artery smooth muscle cell (PASMC) and activated GPD (glycerol-3-phosphate dehydrogenase), linking glycolysis to oxidative phosphorylation and lipid metabolism. Decreased PDH (pyruvate dehydrogenase) activity due to the lipoic acid shortage is compensated by increased fatty acid metabolism and oxidation. PASMC became dependent on extracellular fatty acid sources due to upregulated transporters such as CD36 (cluster of differentiation 36) and CPT (carnitine palmitoyltransferase)-1. Finally, the NFU1 mutation produced a dysregulated antioxidant system in the mitochondria, leading to increased reactive oxygen species levels. PASMC from NFU1 rats showed apoptosis resistance, increased anaplerosis, and attained a highly proliferative phenotype. Attenuation of mitochondrial reactive oxygen species by mitochondrial-targeted antioxidant significantly decreased PASMC proliferation. Conclusions: The alteration in iron-sulfur metabolism completely transforms the proteomic landscape of the mitochondria, leading toward metabolic plasticity and redistribution of energy sources to the acquisition of a proliferative phenotype by the PASMC.

show abstract

Section: Discussionmentioning

confidence: 56%

Single Mutation in the NFU1 Gene Metabolically Reprograms Pulmonary Artery Smooth Muscle Cells

James

Zemskova

Eccles

et al. 2021

ATVB

View full text Add to dashboard Cite

show abstract

“…Xue et al (2017) and Imamura et al (2019) used high fat diets. Douglas et al (2013); Xue et al (2017), and Imamura et al (2019) used transgenic mice Fu et al (2020). reported that IH did not increase IMT of PA (orange arrow).…”

mentioning

confidence: 99%

Effects of Normoxic Recovery on Intima-Media Thickness of Aorta and Pulmonary Artery Following Intermittent Hypoxia in Mice

et al. 2020

View full text Add to dashboard Cite

Obstructive sleep apnea (OSA) patients are at risk for increased blood pressure and carotid intima-media thickness (IMT), with pulmonary hypertension and right-sided heart failure potentially developing as well. Chronic intermittent hypoxia (IH) has been used as an OSA model in animals, but its effects on vascular beds have not been evaluated using objective unbiased tools. Previously published and current experimental data in mice exposed to IH were evaluated for IMT in aorta and pulmonary artery (PA) after IH with or without normoxic recovery using software for meta-analysis, Review Manager 5. Because IMT data reports on PA were extremely scarce, atherosclerotic area percentage from lumen data was also evaluated. IH significantly increased IMT parameters in both aorta and PA as illustrated by Forest plots (P < 0.01), which also confirmed that IMT values after normoxic recovery were within the normal range in both vascular beds. Onesided scarce lower areas in Funnel Plots were seen for both aorta and PA indicating the likelihood of significant publication bias. Forest and Funnel plots, which provide unbiased assessments of published and current data, suggest that IH exposures may induce IMT thickening that may be reversed by normoxic recovery in both aorta and PA. In light of the potential likelihood of publication bias, future studies are needed to confirm or refute the findings. In conclusion, OSA may induce IMT thickening (e.g., aorta and/or PA), but the treatment (e.g., nasal continuous positive airway pressure) will likely lead to improvements in such findings.

show abstract

“…It dismutates the superoxide into hydrogen peroxide, and then the catalase and glutathione peroxidase convert the hydrogen peroxide into water . Down-regulation of SOD2 expression may aggravate pulmonary hypertension . PRDX2 is an endogenous peroxidase, which can reduce oxidative damage in cells, thus reducing cell injury and apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Metabolomics of Artichoke Bud Extract in Spontaneously Hypertensive Rats

Wang

Jiang

Liu³

et al. 2021

ACS Omega

View full text Add to dashboard Cite

Hypertension adversely affects the quality of life in humans across modern society. Studies have attributed increased reactive oxygen species production to the pathophysiology of hypertension. So far, a specific drug to control the disease perfectly has not been developed. However, artichoke, an edible vegetable, plays an essential role in treating many diseases due to its potent antioxidant activities. The objective of this study is to evaluate the effect of artichoke bud extract (ABE) on heart tissue metabolomics of hypertensive rats. Spontaneously hypertensive rats and Wistar–Kyoto (WKY) rats were divided into six groups, then exposed to different doses comprising ABE, Enalapril Maleate, or 1% carboxylmethyl cellulose for 4 weeks. Their blood pressures were recorded at 0, 2, 3, and 4 weeks after the start of the test period. Thereafter, all rats were anesthetized, and blood was collected from their cardiac apexes. Then, we measured the levels for 15 kinds of serum biochemical parameters. An established orthogonal partial least square-discriminant analysis model completed the metabolomic analysis. Hypertensive rats in the ABE group exhibited well-controlled blood pressure, relative to those in the model group. Specifically, artichoke significantly lowered serum levels for total protein (TP), albumin (ALB), and uric acid (UA) in the hypertensive rats. This effect involved the action of eight metabolites, including guanine, 1-methylnicotinamide, p-aminobenzoic acid, NAD, NADH, uridine 5′-monophosphate, adenosine monophosphate, and methylmalonic acid. Collectively, these findings suggest that ABE may play a role in affecting oxidative stress and purine, nicotinate, and nicotinamide metabolism.

show abstract

SOD2 ameliorates pulmonary hypertension in a murine model of sleep apnea via suppressing expression of NLRP3 in CD11b+ cells

Cited by 12 publications

References 41 publications

Single Mutation in the NFU1 Gene Metabolically Reprograms Pulmonary Artery Smooth Muscle Cells

Single Mutation in the NFU1 Gene Metabolically Reprograms Pulmonary Artery Smooth Muscle Cells

Effects of Normoxic Recovery on Intima-Media Thickness of Aorta and Pulmonary Artery Following Intermittent Hypoxia in Mice

Metabolomics of Artichoke Bud Extract in Spontaneously Hypertensive Rats

Contact Info

Product

Resources

About