Mitochondrial DNA: A new driver for sex differences in spontaneous hypertension

Echem, Cinthya; Costa, Tiago J.; Oliveira, Vanessa; Colli, Lucas Giglio; Landgraf, Maristella A.; Rodrigues, S.; Franco, Maria do Carmo Pinho; Landgraf, Richardt Gama; Santos-Eichler, Rosângela Aparecida; Bomfim, Gisele Facholi; Akamine, Eliana Hiromi; Carvalho, Maria Helena Catelli de

doi:10.1016/j.phrs.2019.04.008

Cited by 29 publications

(14 citation statements)

References 37 publications

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“…When found extracellularly, cell-free mtDNA -which can be detected in a range of biological fluids including plasma, serum, urine, and bronchoalveolar lavage fluid (25)(26)(27) -activates neutrophils (22), vascular endothelial cells (28), and alveolar macrophages (29), perpetuating inflammatory signals or cascades. mtDNA has been proposed as a biomarker and prognostic indicator for a range of diseases and syndromes (25,26,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). The source of this extracellular mtDNA is unknown but is assumed to arise from injured cells either in the process of cell death or repair (43).…”

Section: Introductionmentioning

confidence: 99%

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Zhang¹,

Rice²,

Hoffman³

et al. 2020

JCI Insight

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BACKGROUND. Mitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown. METHODS. Cell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters-including FEV 1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure-were examined. RESULTS. U-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.

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Section: Introductionmentioning

confidence: 99%

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Zhang¹,

Rice²,

Hoffman³

et al. 2020

JCI Insight

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“…Mitochondrial DNA is a DAMP that activate TLR9. Echem et al ( 63 ) demonstrated that only male SHR exhibit high levels of plasma mitDNA and the antagonism of TLR9 normalizes mitDNA-induced increased aortic contractions elicited to phenylephrine ( 67 ). TLR9 also negatively modulates cardiac vagal tone and baroreflex in mice ( 68 ).…”

Section: Possible Mechanisms Whereby the Crosstalk Between O-glcnacyl...mentioning

confidence: 99%

O-Linked β-N-Acetylglucosamine Modification: Linking Hypertension and the Immune System

et al. 2022

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The O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of proteins dynamically regulates protein function, localization, stability, and interactions. This post-translational modification is intimately linked to cardiovascular disease, including hypertension. An increasing number of studies suggest that components of innate and adaptive immunity, active players in the pathophysiology of hypertension, are targets for O-GlcNAcylation. In this review, we highlight the potential roles of O-GlcNAcylation in the immune system and discuss how those immune targets of O-GlcNAcylation may contribute to arterial hypertension.

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“…PCR cycle program was carried out in a 9700 Thermocycler (Perkin-Elmer Applied Biosystems, Norwalk, USA). Each fragment had been purified and sequenced by ABI 3730 Sequence Analysis software (Applied Biosystems, Inc., Foster City, CA, USA) using the BigDye Terminator v1.1 kit (ABI Company, Carlsbad, CA, USA), and subsequently SeqWeb program GAP (GCG) was analyzed and compared with the updated consensus Cambridge Sequence [17,18]. Pathogenic mitochondrial variants were identified from the human mitochondrial genome database (https://www.mitomap.org/MITOMAP) [19].…”

Section: Mitochondrial Dna Analysismentioning

confidence: 99%

Associations of mitochondrial DNA 3777–4679 region mutations with maternally inherited essential hypertensive subjects in China

Zhu

You²,

et al. 2020

BMC Med Genet

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Background Nuclear genome or family mitochondrial screening system has become the hot focus of studies into essential hypertension. The role of mitochondrial DNA (mtDNA) in sporadic Chinese patients with hypertension has not been fully understood. The study was to evaluate the associations of mtDNA mutations with maternally inherited essential hypertensive subjects in China. Methods From June 2009 to June 2016, a total of 800 gender-matched Chinese patients with maternally inherited essential hypertension (MIEH) and control group were 1:1 enrolled in this case-control study. Genomic DNA was extracted from each person’s peripheral blood cells. The main mtDNA locations for MIEH were screened with oligodeoxynucleotides 3777-4679 bp, analyzed and compared with the updated consensus Cambridge Sequence. Pathogenic mtDNA mutations were identified from the mitochondrial map. Results MIEH subjects presented significantly higher values than those of control group in abdominal circumference (AC), waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and renal function (P < 0.05). MIEH subjects carried more amino acid changes and coding sequence variants (P < 0.01) than control group. The allele frequencies of the eight single nucleotide polymorphisms (SNPs) were significantly different between the two groups, including m.3970 C > T, m.4048G > A, m.4071C > T, m.4086C > T, m. 4164A > G and m.4248 T > C in ND1 gene, and m.4386 T > C and m.4394C > T in tRNAGln gene(P < 0.001). Fifty-five homoplasmic or heteroplasmic mutations were detected in 5 genes: ND1, tRNAIle, tRNAMet, tRNAGln and ND2 gene. The ND1 gene was the main mutation site, where the most mtDNA mutation was m.3970 C > T. Conclusions The mtDNA mutations were involved in the process of MIEH. We identified mitochondrial genetic characteristics in MIEH patients in China. The present research serves as a solid foundation for further detailed research on the association between MIEH and mitochondrial dysfunction, and their causal relationship in Chinese and other populations with a similar lifestyle.

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Mitochondrial DNA: A new driver for sex differences in spontaneous hypertension

Cited by 29 publications

References 37 publications

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

O-Linked β-N-Acetylglucosamine Modification: Linking Hypertension and the Immune System

Associations of mitochondrial DNA 3777–4679 region mutations with maternally inherited essential hypertensive subjects in China

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