Genetic and epigenetic regulation of abdominal aortic aneurysms

Mangum, Kevin; Farber, Mark A.

doi:10.1111/cge.13705

Cited by 37 publications

(30 citation statements)

References 137 publications

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“…MiRNAs are short (~20 base pair long), single-stranded non-coding RNA that directly regulate gene expression and exert a wide range of cellular functions [ 78 ]. They negatively regulate gene expression by degrading mRNA or mimicking small interfering RNA (siRNA) and inhibiting translation.…”

Section: Vsmc-mediated Extracellular Matrix Production and Degradamentioning

confidence: 99%

“…miRNAs are initially transcribed as pi-miRNAs, longer primary transcripts, that are processed by the ribonuclease enzyme complex Drosha/DGCR8, followed by Dicer, and incorporation into the RNA-induced silencing complex (RISC) [ 79 ]. Mature miRNA is able to pair with a highly conserved seed sequence within the 3’ untranslated region (UTR) of potentially multiple target genes [ 78 ]. A wide variety of miRNAs have been studied in AAA that target specific genes to regulate VSMC plasticity as well as ECM degradation and inflammation ( Table 2 ).…”

Section: Vsmc-mediated Extracellular Matrix Production and Degradamentioning

confidence: 99%

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Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

Gurung

Choong

Woo

et al. 2020

IJMS

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Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.

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Section: Vsmc-mediated Extracellular Matrix Production and Degradamentioning

confidence: 99%

Section: Vsmc-mediated Extracellular Matrix Production and Degradamentioning

confidence: 99%

Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

Gurung

Choong

Woo

et al. 2020

IJMS

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“…An abdominal aortic aneurysm (AAA) is a pathological enlargement of the infrarenal aorta that can potentially be life‐threatening if progressing to rupture 1,2 . An important aspect of AAA formation and progression, apart from host genetic background and lifestyle factors (e.g., diet, smoking), are environmental factors, which are crucial in the regulation of inflammatory processes 3–5 . Several studies have suggested that bacterial and viral pathogens, as well as host response, may be involved in the formation of AAA and/or accelerate its progression 6–22 .…”

Section: Introductionmentioning

confidence: 99%

Abdominal aortic aneurysm and virus infection: A potential causative role for cytomegalovirus infection?

Jabłońska

Zagrapan

Paradowska

et al. 2021

Journal of Medical Virology

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An abdominal aortic aneurysm (AAA) is a multifactorial disease with a variety of genetic and environmental risk factors, but the exact mechanism of AAA formation and progression is still not well understood. The present study investigated the frequency of cytomegalovirus (CMV), Epstein‐Barr virus (EBV), and papillomavirus types 6 and 11 (HPV6 and HPV11), their impact on clinical manifestations of cardiovascular diseases, and their possible association with inflammation in patients with AAA and healthy volunteers. Genotyping of CMV UL75, EBV LMP‐1, and HPV6, and HPV11 E6 was performed by polymerase chain reaction (PCR), while the viral DNA loads were measured by quantitative real‐time PCR. Cytokine levels were determined by enzyme‐linked immunosorbent assays. The CMV UL75 was detected more frequently in the blood of patients with AAA than in the blood of healthy volunteers (32.7% vs. 6.3%, p < .0001). Neither EBV LMP‐1 nor HPV6 E6 was found in blood and aortic wall biopsies, while the HPV11 E6 was detected in 36.4% of AAA walls. The CMV infection in patients with AAA was associated with an increased risk of hypertension and coronary artery disease (OR, 9.057; 95% CI, 1.141–71.862; p = .037; and OR, 2.575; 95% CI, 1.002–6.615; p = .049, respectively). Additionally, CMV‐infected patients with AAA had higher tumor necrosis factor‐α levels compared with noninfected subjects (p = .017). Our findings suggest that CMV infection can stimulate local inflammation in the aorta but is not a direct cause of most abdominal aortic aneurysms.

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“…AAA has been attributed to many environmental and genetic factors. 7 Genetic studies have identified many novel loci for AAA. [8][9][10][11] Although the pathogenesis of AAA is unclear, accumulating evidence supports a central role for inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…AAA has been attributed to many environmental and genetic factors. 7 Genetic studies have identified many novel loci for AAA. 8–11 …”

Section: Introductionmentioning

confidence: 99%

Smoking, Hypertension, and GG Genotype of the IL-6 rs1800796 Polymorphism are Independent Risk Factors for Abdominal Aortic Aneurysm in Han Population

Zhang

Wang

2021

PGPM

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Background: Recent researches have investigated the link between the rs1800796 polymorphism (−572G/C) in the interleukin-6 (IL-6) gene and the risk of abdominal aortic aneurysm (AAA). However, no Chinese studies have addressed the association between the risk of AAA and this polymorphism. Methods: This case-control study included 153 AAA patients and 205 controls. Diabetes mellitus, hypertension, dyslipidemia, and coronary artery disease (CAD) status were collected. The AAA and control groups were 69.20 ± 7.56 and 68.50 ± 7.12 years old, respectively. Results: The analysis revealed that the G allele and GG genotype of the IL-6 rs1800796 polymorphism were remarkedly correlated with an elevated risk of AAA. The GG genotype displayed an association with the risk of AAA after adjustment for gender, body mass index, age, drinking, and smoking. Subgroup analyses indicated that this polymorphism elevated the risk of AAA among males, individuals aged ≥70 years, smokers, drinkers, individuals with a body mass index (BMI) ≥25 kg/m 2 , patients without diabetes, and patients with hypertension. Univariate and multivariate analyses indicated that smoking, hypertension, and the GG genotype (rs1800796 polymorphism) were independently related with the risk of AAA. Conclusion:The IL-6 rs1800796 polymorphism increases the risk of AAA. In addition, smoking, hypertension, and the GG genotype of the rs1800796 polymorphism are independent risk factors for AAA. Further studies of Chinese populations are needed to validate these findings.

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Genetic and epigenetic regulation of abdominal aortic aneurysms

Cited by 37 publications

References 137 publications

Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

Abdominal aortic aneurysm and virus infection: A potential causative role for cytomegalovirus infection?

Smoking, Hypertension, and GG Genotype of the IL-6 rs1800796 Polymorphism are Independent Risk Factors for Abdominal Aortic Aneurysm in Han Population

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