Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms.
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ABSTRACT:
SUBMITTER: Sugiyama K
PROVIDER: S-EPMC8149374 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Thoracic Aortic Aneurysm (TAA) is characterized by the dilation and degradation of the aorta and is fatal if not diagnosed and treated appropriately. There are no specific clinical symptoms, so better knowledge of the physiopathology of TAAs and their underlying genetic mechanisms is needed to improve diagnosis and therapy. MiRNAs regulate gene expression post-transcriptionally and are known to be involved in cerebrovascular disease. The current study aimed to identify differentially expressed miRNAs in patients with TAAs and determine whether their predicted target genes could be associated with this condition. Nanostring assays identified miRNAs in plasma and tissue samples from four TAA patients. RT-PCR validated the expression levels of these miRNAs in a further 22 plasma samples. Three, hsa-miR140-5p, hsa-miR-191-5p and hsa-miR-214-3p showed significant expression level differences between plasma samples collected pre- and post-surgically from each patient. Analyses of the predicted target gene controlled by these miRNAs revealed nine genes whose expression was investigated in the same 22 plasma samples. The gene expression levels were inversely correlated with the expression of their respective miRNAs. From these, CCND2, CRKL, HEY1, MTMR4, NFIA and PPP1CB, showed fold-change differences >1.5 between the two plasma samples. An in-depth literature search and Cytoscape software three genes; MTMR4, NFIA and PPP1CB, showed a possible association with the TGF-β signalling pathway. It is suggested that the three miRNAs detected together with their target genes could play a role in the TGF-β signalling pathway and thus be involved in TAA pathogenesis.
2020-05-29 | GSE151378 | GEO
Project description:Thoracic Aortic Aneurysm (TAA) is characterized by the dilation of the aorta and is fatal if not diagnosed and treated appropriately. The underlying genetic mechanisms have not been completely delineated, so better knowledge of the physiopathology of TAAs is needed to improve detection and therapy. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and are known to be involved in cardiovascular diseases (CVDs). The current study aimed to identify miRNAs that can be used as possible biomarkers for the early diagnosis of patients with ascending TAAs (ATAAs). MiRNA expression was profiled by NanoString nCounter technology using 12 samples including tissue and pre- and post-surgical plasma from ATAA patients. Four miRNAs were selected and further validated by real time polymerase chain reaction (RT-PCR) in 22 plasma samples from which three miRNAs (hsa-miR140-5p, hsa-miR-191-5p and hsa-miR-214-3p) showed significant expression level differences between the two types of plasma samples. Further analyses of the corresponding predicted target genes by these miRNAs, revealed two genes (Myotubularin-related protein 4 (MTMR4) and Phosphatase 1 catalytic subunit ? (PPP1CB)) whose expression was inversely correlated with the expression of their respective miRNAs. Overall, in this pilot study, we identified three miRNAs that might serve as potential biomarkers and therapeutic targets in ATAA.
| S-EPMC7385583 | biostudies-literature
Project description:Degenerative aneurysms of the thoracic aorta are increasing in prevalence; open repair of descending thoracic aortic aneurysms is associated with high rates of morbidity and mortality. Repair of isolated descending thoracic aortic aneurysms using stent grafts was introduced in 1995, and in an anatomically suitable subgroup of patients with thoracic aortic aneurysm, repair with endovascular stent graft provides favorable outcomes, with decreased perioperative morbidity and mortality relative to open repair. The cornerstones of successful thoracic endovascular aneurysm repair are appropriate patient selection, thorough preprocedural planning, and cautious procedural execution, the elements of which are discussed here.
| S-EPMC3140248 | biostudies-other
Project description:MiRNA analysis in Thoracic Aortic aneurysms
| PRJNA635645 | ENA
Project description:AimsTo observe, describe, and evaluate management and timing of intervention for patients with untreated thoracic aortic aneurysms.Methods and resultsProspective study of UK National Health Service (NHS) patients aged ≥18 years, with new/existing arch or descending thoracic aortic aneurysms of ≥4 cm diameter, followed up until death, intervention, withdrawal, or July 2019. Outcomes were aneurysm growth, survival, quality of life (using the EQ-5D-5L utility index), and hospital admissions. Between 2014 and 2018, 886 patients were recruited from 30 NHS vascular/cardiothoracic units. Maximum aneurysm diameter was in the descending aorta in 725 (82%) patients, growing at 0.2 cm (0.17-0.24) per year. Aneurysms of ≥4 cm in the arch increased by 0.07 cm (0.02-0.12) per year. Baseline diameter was related to age and comorbidities, and no clinical correlates of growth were found. During follow-up, 129 patients died, 64 from aneurysm-related events. Adjusting for age, sex, and New York Heart Association dyspnoea index, risk of death increased with aneurysm size at baseline [hazard ratio (HR): 1.88 (95% confidence interval: 1.64-2.16) per cm, P < 0.001] and with growth [HR: 2.02 (1.70-2.41) per cm, P < 0.001]. Hospital admissions increased with aneurysm size [relative risk: 1.21 (1.05-1.38) per cm, P = 0.008]. Quality of life decreased annually for each 10-year increase in age [-0.013 (-0.019 to -0.007), P < 0.001] and for current smoking [-0.043 (-0.064 to -0.023), P = 0.004]. Aneurysm size was not associated with change in quality of life.ConclusionInternational guidelines should consider increasing monitoring intervals to 12 months for small aneurysms and increasing intervention thresholds. Individualized decisions about surveillance/intervention should consider age, sex, size, growth, patient characteristics, and surgical risk.
| S-EPMC9246658 | biostudies-literature
Project description:BackgroundAortic aneurysm is an increasingly common vascular disorder with fatal implication. However, there is no established diagnosis other than that based on aneurysmal size. For this purpose, serum protein biomarkers for aortic aneurysms are valuable. Although most of the studies on serum biomarker discovery have been based on comparison of serum proteins from the patient group with those from the healthy group, we considered that comparison of serial protein profiles such as those in presurgical and postsurgical sera within one patient would facilitate identification of biomarkers since the variability of serial protein profiles within one patient is smaller than that between groups. In this study, we examined serum proteins with differential levels in postsurgery compared with those in presurgery after the removal of aneurysmal tissues in abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA) patients in order to identify potential serum biomarkers for AAAs and TAAs.ResultsA proteomic approach with an isobaric tag for relative and absolute quantitation (iTRAQ) labeling followed by nano liquid chromatography (nanoLC)-matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF/TOF)-tandem mass spectrometry (MS/MS) was used. In the sera of patients with AAAs and TAAs, a total of 63 and 71 proteins with differential levels were further narrowed down to 6 and 8 increased proteins (≧1.3 fold, postsurgical vs. presurgical) (p < 0.05, patient vs. control) and 12 and 17 decreased proteins (< 0.77 fold, postsurgical vs. presurgical) (p < 0.05, patient vs. control) in postsurgical sera compared with those in presurgical sera, respectively. All of the increased proteins in postsurgical sera of both AAA and TAA patients included several known acute-phase proteins. On the other hand, in the decreased proteins, we found intriguing molecules such as α-2-macroglobulin, gelsolin, kallistatin, and so on. Among them, we confirmed that kallistatin in both AAA and TAA patients and α-2-macroglobulin in TAA patients showed decrease levels in postsurgical sera similar to those in control sera by Western blot analysis with other sera from AAA and TAA patients.ConclusionsTaken together, our findings suggest that Kallistatin and α-2-macroglobulin are potential serum biomarkers for both AAA and TAA and TAA, respectively.
| S-EPMC3698092 | biostudies-literature
Project description:Up to 20% of individuals who have thoracic aortic aneurysms or acute aortic dissections but who do not have syndromic features have a family history of thoracic aortic disease. Significant genetic heterogeneity is established for this familial condition. Whole-genome linkage analysis and exome sequencing of distant relatives from a large family with autosomal-dominant inheritance of thoracic aortic aneurysms variably associated with the bicuspid aortic valve was used for identification of additional genes predisposing individuals to this condition. A rare variant, c.1031A>C (p.Glu344Ala), was identified in MAT2A, which encodes methionine adenosyltransferase II alpha (MAT IIα). This variant segregated with disease in the family, and Sanger sequencing of DNA from affected probands from unrelated families with thoracic aortic disease identified another MAT2A rare variant, c.1067G>A (p.Arg356His). Evidence that these variants predispose individuals to thoracic aortic aneurysms and dissections includes the following: there is a paucity of rare variants in MAT2A in the population; amino acids Glu344 and Arg356 are conserved from humans to zebrafish; and substitutions of these amino acids in MAT Iα are found in individuals with hypermethioninemia. Structural analysis suggested that p.Glu344Ala and p.Arg356His disrupt MAT IIα enzyme function. Knockdown of mat2aa in zebrafish via morpholino oligomers disrupted cardiovascular development. Co-transfected wild-type human MAT2A mRNA rescued defects of zebrafish cardiovascular development at significantly higher levels than mRNA edited to express either the Glu344 or Arg356 mutants, providing further evidence that the p.Glu344Ala and p.Arg356His substitutions impair MAT IIα function. The data presented here support the conclusion that rare genetic variants in MAT2A predispose individuals to thoracic aortic disease.
| S-EPMC4289682 | biostudies-literature
Project description:There has been increasing evidence that ascending thoracic aortic aneurysms (TAAs) protect against atherosclerosis. However, there have been no studies examining the relationship between ascending TAAs and clinical endpoints of atherosclerosis, such as stroke or peripheral arterial disease. In this study, we aim to characterize the relationship between TAAs and a specific clinical endpoint of atherosclerosis, myocardial infarction (MI). We compared prevalence of coronary artery disease (CAD) and MIs in 487 patients who underwent surgical repair for ascending TAAs to 500 control patients who did not have an ascending TAA. Multivariate binary logistic regression was used to calculate the odds of having MI if a patient had an ascending TAA versus any of several MI risk factors. There was a significantly lower prevalence of CAD and MI in the ascending TAA group than in the control TAA group. The odds of having a MI if a patient had a MI risk factor were all > 1 (more likely to have a MI), with the lowest statistically significant odds ratio being 1.54 (age; p = 0.001) and the highest being 14.9 (family history of MI; p < 0.001). The odds ratio of having a MI if a patient had an ascending TAA, however, was near 0 at 0.05 (p < 0.001). This study provides evidence that ascending TAAs protect against MIs, adding further support to the hypothesis that ascending TAAs protect against atherosclerotic disease.
| S-EPMC4169096 | biostudies-other
Project description:ObjectivesCurrent endografts for thoracic endovascular aortic repair (TEVAR) are much stiffer than the aorta and have been shown to induce acute stiffening. In this study, we aimed to estimate the impact of TEVAR on left ventricular (LV) stroke work (SW) and mass using a non-invasive image-based workflow.MethodsThe University of Michigan database was searched for patients treated with TEVAR for descending aortic pathologies (2013-2016). Patients with available pre-TEVAR and post-TEVAR computed tomography angiography and echocardiography data were selected. LV SW was estimated via patient-specific fluid-structure interaction analyses. LV remodelling was quantified through morphological measurements using echocardiography and electrocardiographic-gated computed tomography angiography data.ResultsEight subjects were included in this study, the mean age of the patients was 68 (73, 25) years, and 6 patients were women. All patients were prescribed antihypertensive drugs following TEVAR. The fluid-structure interaction simulations computed a 26% increase in LV SW post-TEVAR [0.94 (0.89, 0.34) J to 1.18 (1.11, 0.65) J, P = 0.012]. Morphological measurements revealed an increase in the LV mass index post-TEVAR of +26% in echocardiography [72 (73, 17) g/m2 to 91 (87, 26) g/m2, P = 0.017] and +15% in computed tomography angiography [52 (46, 29) g/m2 to 60 (57, 22) g/m2, P = 0.043]. The post- to pre-TEVAR LV mass index ratio was positively correlated with the post- to pre-TEVAR ratios of SW and the mean blood pressure (ρ = 0.690, P = 0.058 and ρ = 0.786, P = 0.021, respectively).ConclusionsTEVAR was associated with increased LV SW and mass during follow-up. Medical device manufacturers should develop more compliant devices to reduce the stiffness mismatch with the aorta. Additionally, intensive antihypertensive management is needed to control blood pressure post-TEVAR.
| S-EPMC6537936 | biostudies-literature
Project description:Aortic aneurysms are common among the elderly population. A large majority of aortic aneurysms are located at two distinct aneurysm-prone regions, the abdominal aorta and thoracic aorta involving the ascending aorta. In this study, we combined two factors that are associated with human aortic aneurysms, hypertension and degeneration of elastic lamina, to induce an aortic aneurysm in mice. Roles of hemodynamic conditions in the formation of aortic aneurysms were assessed using two different methods for inducing hypertension and antihypertensive agents. In 9-week-old C57BL/6J male mice, hypertension was induced by angiotensin II or deoxycorticosterone acetate-salt hypertension; degeneration of elastic lamina was induced by infusion of beta-aminopropionitrile, a lysyl oxidase inhibitor. Irrespective of the methods for inducing hypertension, mice developed thoracic and abdominal aortic aneurysms (38% to 50% and 30 to 49%, respectively). Aneurysms were found at the two aneurysm-prone regions with site-specific morphological and histological characteristics. Treatment with an antihypertensive agent, amlodipine, normalized blood pressure and dramatically reduced aneurysm formation in the mice that received angiotensin II and beta-aminopropionitrile. However, treatment with captopril, an angiotensin-converting enzyme inhibitor, did not affect blood pressure or the incidence of aortic aneurysms in the mice that received deoxycorticosterone acetate-salt and beta-aminopropionitrile. In summary, we have shown that a combination of hypertension and pharmacologically induced degeneration of elastic laminas can induce both thoracic and abdominal aortic aneurysms with site-specific characteristics. The aneurysm formation in this model depended on hypertension but not on direct effects of angiotensin II to the vascular wall.
| S-EPMC2859958 | biostudies-literature