Circulating biomarkers associated with aortic diameter in male and female patients with thoracic aortic disease: a cross-sectional study

Meccanici, Frederike; Thijssen, Carlijn G E; Dekker, Silvy; Bons, Lidia R.; Gökalp, Arjen L.; Rijke, Yolanda B. de; Takkenberg, Johanna J.M.; Mokhles, Mostafa M; Bekkers, Jos A.; Boersma, Eric; Bouwens, Elke; Bosch, Annemien E. van den; Kimmenade, Roland R L van; Roos‐Hesselink, Jolien W.

doi:10.1136/openhrt-2023-002317

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…In this cross-sectional study, the blood of 158 patients with ATAAD was analyzed, and several circulating blood biomarkers were associated with the maximal thoracic aortic diameter estimated by CT-angiography or transthoracic echocardiography. The biomarkers that were found to be significantly associated with aortic size were primarily inflammatory markers IL-6 and GDF-15 [ 135 ]. Another study associated elevated levels of TLT-2 expressed in cells of the immune system [ 200 ] and IL-11[ 226 ] with ATAAD.…”

Section: Sporadic and Genetic Biomarkers In Ataa(d)mentioning

confidence: 99%

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections

Ganizada,

Veltrop,

Akbulut

et al. 2024

Basic Res Cardiol

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Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM–VSMC network.

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Section: Sporadic and Genetic Biomarkers In Ataa(d)mentioning

confidence: 99%

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections

Ganizada,

Veltrop,

Akbulut

et al. 2024

Basic Res Cardiol

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show abstract

“…Despite the devastating clinical presentation, clinical outcomes for this cohort have seen little improvement over the last 15 years ( 3 ). Diagnosis without cross sectional imaging is challenging and is compounded by the lack of a TAD specific biomarker ( 4 ). Importantly, there are no pharmaceutical treatments which prevent aneurysm formation or progression effectively, with current focus on reducing biomechanical loading of the aorta through antihypertensives.…”

Section: Introductionmentioning

confidence: 99%

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

Singh,

Shetty,

Jacob

et al. 2024

Front. Cardiovasc. Med.

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Thoracic aortic disease (TAD) is often silent until a life-threatening complication occurs. However, genetic information can inform both identification and treatment at an early stage. Indeed, a diagnosis is important for personalised surveillance and intervention plans, as well as cascade screening of family members. Currently, only 20% of heritable TAD patients have a causative mutation identified and, consequently, further advances in genetic coverage are required to define the remaining molecular landscape. The rapid expansion of next generation sequencing technologies is providing a huge resource of genetic data, but a critical issue remains in functionally validating these findings. Induced pluripotent stem cells (iPSCs) are patient-derived, reprogrammed cell lines which allow mechanistic insights, complex modelling of genetic disease and a platform to study aortic genetic variants. This review will address the need for iPSCs as a frontline diagnostic tool to evaluate variants identified by genomic discovery studies and explore their evolving role in biological insight through to drug discovery.

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Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics: secondary analyses based on the prospective BELIEVE cohort study

Sofíudóttir,

Munk,

Christensen

et al. 2024

Rheumatol Int

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Background Currently, there are no reliable biomarkers for predicting treatment response in chronic inflammatory diseases (CIDs). Objective To determine whether serum microfibrillar-associated protein 4 (MFAP4) levels can predict the treatment response to biological therapy in patients with CIDs. Methods The BELIEVE study was originally designed as a prospective, multi-center cohort study of 233 patients with either rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, Crohn’s disease, or ulcerative colitis, initiating treatment with a biologic agent (or switching to another). Clinical assessment and blood sample collection were performed at baseline and 14–16 weeks after treatment initiation. The primary analyses included participants with available blood samples at baseline; missing data were handled as non-responders. The patients were stratified into the upper tertile of serum MFAP4 (High MFAP4) versus a combined category of middle and lower tertiles (Other MFAP4). The primary outcome was the proportion of patients with clinical response to biologic therapy after 14–16 weeks. Results 211 patients were included in the primary analysis population. The mean age was 43.7 (SD: 14.8) years, and 120 (59%) were female. Positive treatment response was observed in 41 (59%) and 69 (49%) for High MFAP4 and Other MFAP4, respectively. When adjusting for pre-specified variables (CID, age, sex, smoking status, and BMI), the adjusted OR was 2.28 (95% CI: 1.07 to 4.85) for a positive treatment outcome in the High MFAP4 group. Conclusion A high MFAP4 status before initiating biological treatment is associated with a positive clinical response, when adjusting for confounding factors.

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Circulating biomarkers associated with aortic diameter in male and female patients with thoracic aortic disease: a cross-sectional study

Cited by 4 publications

References 31 publications

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics: secondary analyses based on the prospective BELIEVE cohort study

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