Biomarkers in TAA—The Holy Grail

Bogerijen, Guido H.W. van; Tolenaar, Jip L.; Grassi, Viviana; Lomazzi, Chiara; Segreti, Sara; Rampoldi, Vincenzo; Elefteriades, John A.; Trimarchi, Santi

doi:10.1016/j.pcad.2013.05.004

Cited by 29 publications

(27 citation statements)

References 65 publications

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“…Accordingly, we observed significant increased amounts of CD3 + CD4 + CD8 + CD68 + CD20 + cells in tissue aorta samples from patients with Stanford type A aortic dissection [32]. Increased plasma levels of inflammatory markers, such as C-reactive protein (CRP) and inflammatory cytokines have been observed in aortic dissection and sporadic TAA patients [48]. In accordance with these data, we assessed higher plasma levels of Interleukin-(IL-) 6, Tumor necrosis factor-α (TNF-α), Interferon (INF)-γ, CRP, MMP-2 and-9 plasma levels in Stanford type A aortic dissection and sporadic TAA patients than controls (12.66 ± 2.1 vs. 3.1 ± 0.99, P b 0.001; 16.78 ± 1.2 vs. 7.1 ± 2.2, P b 0.0001; 12.13 ± 1.7 vs. 2.1 ± 0.5 P b 0.0001; 14.66 ± 3.2 vs. 4.6 ± 1.67, P b 0.0001; 56.8 ± 3.8 vs. 12.54 ± 1.6, P b 0.0001; and 59.7 ± 3.7 vs. 11.7 ± 2.6, P b 0.0001, respectively) [32].…”

Section: Focus On the Role In Sporadic Taad Of Genetic Variants In Pamentioning

confidence: 84%

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Balistreri

2015

Vascular Pharmacology

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Keywords:Sporadic thoracic aortic aneurysms (TAA) and dissections Genetic variants Biomarkers Targets for new personalized therapeutic treatments Sporadic thoracic aortic aneurysms (TAA) and dissections are one of the major causes of morbidity and mortality worldwide, especially in those older than 65 years. The presentation of TAA is varied and often silent. Thus, sporadic TAA detection is often fortuitous, with identification occurring during a routine physical examination or during an unrelated medical evaluation. Once suspected, confirmation by imaging clinical approaches is needed to allow the choose of the unique treatments for TAA, namely the surgery procedures, including elective surgery or endovascular repair before the onset of catastrophic and fatal complications, such as dissection or rupture. At present, there are no biomarkers available to identify TAAs before visible symptoms. However, recent progresses in understanding of molecular and cellular mechanisms involved in the patho-physiology of sporadic TAA are suggesting different molecular pathways and their genetic variants as potential biomarkers, which might be applied into TAA clinical practice in the near future. Here, we report literature evidence on some disease pathways and their genetic variants on TAA susceptibility and compliances, and their translation as promising TAA preventive and prognostic biomarkers and targets for new personalized therapeutic treatments.

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Section: Focus On the Role In Sporadic Taad Of Genetic Variants In Pamentioning

confidence: 84%

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Balistreri

2015

Vascular Pharmacology

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“…Targeting surgical therapy better should be an additional direction of future research. Genetic and epigenetic markers of AAA or TAA growth have not been adequately investigated to date in studies with a sufficient amount of patients that would allow specificity and sensitivity levels to be assessed 58 61. Future work should focus on using simple serological tests (such as inflammatory markers or structural proteins of the aortic wall) as markers of growth in order to offer surgical treatment earlier.…”

Section: Discussionmentioning

confidence: 99%

The genetic basis for aortic aneurysmal disease

Saratzis

Bown

2014

Heart

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Aortic aneurysms are an important cause of cardiovascular death in elderly patients. At present, little is known of the pathobiology of aneurysmal disease and this limits the ability to develop non-surgical treatments to stabilise aneurysms. Both thoracic and abdominal aortic aneurysms (AAA) demonstrate a strong genetic component in their aetiology. Determination of the genetic variants associated with aneurysmal disease is one approach to increasing the understanding the pathways leading to aneurysmal degeneration of the aorta. In this review, we aim to summarise the current knowledge of the genetics underlying the two most common disease phenotypes, thoracic aortic aneurysm (TAA) and AAA. Genetically, AAA represent a multifactorial disease, with the likelihood that there are multiple variants of very low effect sizes contributing to the overall genetic disease risk. Non-syndromic TAA appears to be associated with a smaller number of risk loci with higher individual effect sizes at these loci. Candidate gene and genome-wide approaches have identified robust associations between AAA and variants in/nearby the SORT1, low-density lipoprotein receptor, DAB2IP, LRP1, ELN, CRP, TGFB and various matrix metallo-proteinase genes suggesting that aberrations of lipid metabolism and proteolytic pathways are the key contributors to disease. Some of these associations (eg, LRP1) are not associated with atherosclerosis, suggesting pathways unique to AAA. Genetic variants associated with non-syndromic TAA (ACTA2 and MYH11) are related to the TGFβ pathway, strongly implicated in syndromic TAA, thus suggesting a common pathway between syndromic and non-syndromic TAA.

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“…5 -9 These data nourish hope that tsTGF-β1 may serve as a biomarker of MFS. 10 Interestingly, TGF-β1 signaling is also involved in other genetic aortic syndromes (GAS), such as Loeys-Dietz syndrome (LDS) caused by mutations of TGFBR1, TGFBR2, or TGFB2, 11,12 isolated thoracic aortic aneurysm and dissection (TAAD) caused by mutations in ACTA2, SMAD3, or MYH11, 13 and bicuspid aortic valve disease (BAVD), which in rare cases is caused by mutations in the NOTCH1 gene.…”

Section: Introductionmentioning

confidence: 99%

Total Serum Transforming Growth Factor‐β1 Is Elevated in the Entire Spectrum of Genetic Aortic Syndromes

Hillebrand

Millot

Sheikhzadeh

et al. 2014

Clinical Cardiology

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Background: Total serum transforming growth factor-beta 1 (tsTGF-β1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD). Hypothesis: tsTGF-β1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD. Methods: We measured tsTGF-β1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317 consecutive patients with suspected or known genetic aortic syndrome (167 men, 150 women; mean age 43 ± 14 years). TAAD was diagnosed in 20, LDS in 20, MFS in 128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119 patients. Results: Elevated tsTGF-β1 levels were associated with causative gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic syndrome qualified as an independent predictor of tsTGF-β1 (P = 0.001). The tsTGF-β1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P = 0.015). Similarly, tsTGF-β1 levels were elevated in MFS (P = 0.003) and in BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to specific clinical features of MFS, FBN1 in-frame mutations (P = 0.019) were associated with increased tsTGF-β1 levels. Conclusions: tsTGF-β1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-β1 levels may mirror different degrees of alteration of tsTGF-β1 signaling in different genetic aortic syndromes.

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Biomarkers in TAA—The Holy Grail

Cited by 29 publications

References 65 publications

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

The genetic basis for aortic aneurysmal disease

Total Serum Transforming Growth Factor‐β1 Is Elevated in the Entire Spectrum of Genetic Aortic Syndromes

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