Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension

Simão, Vinícius Augusto; Ferder, León; Manucha, Walter; Chuffa, Luiz Gustavo de Almeida

doi:10.1007/s11906-022-01214-4

Cited by 7 publications

(4 citation statements)

References 151 publications

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“…Endothelial cells (ECs) and VSMCs are important components in regulating the contraction and relaxation function and structure of artery. Inflammatory mechanisms are involved in endothelial dysfunction, and mtDNA acts as an important stimuli of inflammatory activation ( Simão et al, 2022 ). Mao Y et al reported that in palmitic acid treated ECs, the expression levels of pro-inflammatory factors such as MCP1, IFN-γ, IL-1, and adhesion factors ICAM-1 were significantly increased, which enhanced the adhesion of monocytes to ECs.…”

Section: The Role Of Mitochondrial Dna In Cardiovascular Diseasesmentioning

confidence: 99%

Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases

Ding,

Chen,

Zhao

et al. 2024

Front. Cell Dev. Biol.

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Mitochondrial dysfunction is one of the hallmarks of cardiovascular aging. The leakage of mitochondrial DNA (mtDNA) is increased in senescent cells, which are resistant to programmed cell death such as apoptosis. Due to its similarity to prokaryotic DNA, mtDNA could be recognized by cellular DNA sensors and trigger innate immune responses, resulting in chronic inflammatory conditions during aging. The mechanisms include cGAS-STING signaling, TLR-9 and inflammasomes activation. Mitochondrial quality controls such as mitophagy could prevent mitochondria from triggering harmful inflammatory responses, but when this homeostasis is out of balance, mtDNA-induced inflammation could become pathogenic and contribute to age-related cardiovascular diseases. Here, we summarize recent studies on mechanisms by which mtDNA promotes inflammation and aging-related cardiovascular diseases, and discuss the potential value of mtDNA in early screening and as therapeutic targets.

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Section: The Role Of Mitochondrial Dna In Cardiovascular Diseasesmentioning

confidence: 99%

Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases

Ding,

Chen,

Zhao

et al. 2024

Front. Cell Dev. Biol.

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“…Mechanisms of DNA damage and repair have been deeply investigated to explain the consequences of damages on health, to investigate the possibility to restore physiological status of damaged cells, and to assess their association with disorders and pathological conditions. Numerous studies, brilliantly overviewed by Schumacher and colleagues [67], have investigated these processes from several perspectives, pointing out a tight relation between molecular [68], cellular [69], and systemic [70] levels. Specifically, at the molecular level, DNA damage can lead to genomic instability, telomeric dysfunction, epigenetic alterations, deregulation of transcription patterns, proteostatic stress and mitochondrial dysfunction; at the cellular level, stem cell exhaustion and cellular senescence; systemic repercussions regard complex processes as signalling, inflammation and sensing.…”

Section: Genomic (In)stability In Homo Sapiens: Just a Matter Of Luck?mentioning

confidence: 99%

Genomic Instability Evolutionary Footprints on Human Health: Driving Forces or Side Effects?

Veschetti

Treccani

Tomi

et al. 2023

IJMS

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In this work, we propose a comprehensive perspective on genomic instability comprising not only the accumulation of mutations but also telomeric shortening, epigenetic alterations and other mechanisms that could contribute to genomic information conservation or corruption. First, we present mechanisms playing a role in genomic instability across the kingdoms of life. Then, we explore the impact of genomic instability on the human being across its evolutionary history and on present-day human health, with a particular focus on aging and complex disorders. Finally, we discuss the role of non-coding RNAs, highlighting future approaches for a better living and an expanded healthy lifespan.

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“…The result is a persistent increase of blood glucose levels (hyperglycemia) leading to micro- and macro-vascular generalized damages (nephropathy, neuropathy, maculopathy, central and peripheral vasculopathy) ( 14 ). The etiopathogenesis of primary HT include alterations in the activity of sympathetic nervous system, the renin-angiotensin system, the pathways involved in calcium and sodium homeostasis, the structure and reactivity of the vascular smooth muscle network ( 15 – 17 ). However, both T2D and HT are multigenic diseases where several genetic/epigenetic factors (including genetic polymorphisms) may concur to determine heterogeneous phenotypes ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival

Ottaiano

Santorsola

Circelli³

et al. 2023

Front. Med.

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IntroductionWe studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.Patients and methodsT2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P < 0.05 were considered statistically significant.ResultsTwo-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P < 0.05). At multivariate analysis, age (≥65 vs. <65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40–8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (>25 kg/m2) associated with occurrence of p53 mutations (P < 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).ConclusionDiabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence.

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Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension

Cited by 7 publications

References 151 publications

Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases

Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases

Genomic Instability Evolutionary Footprints on Human Health: Driving Forces or Side Effects?

Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival

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