MicroRNAs (miRNAs) are critical regulators of the functional pathways involved in the pathogenesis of cardiovascular diseases. Understanding of the disease-associated alterations in tissue and plasma will elucidate the roles of miRNA in modulation of gene expression throughout development of sporadic non-syndromic ascending thoracic aortic aneurysm (TAA). This will allow one to propose relevant biomarkers for diagnosis or new therapeutic targets for the treatment. The high-throughput sequencing revealed 20 and 17 TAA-specific miRNAs in tissue and plasma samples, respectively. qRT-PCR analysis in extended cohort revealed sex-related differences in miR-10a-5p, miR-126-3p, miR-155-5p and miR-148a-3p expression, which were the most significantly dysregulated in TAA tissues of male patients. Unexpectedly, the set of aneurysm-related miRNAs in TAA plasma did not resemble the tissue signature suggesting more complex organism response to the disease. Three of TAA-specific plasma miRNAs were found to be restored to normal level after aortic surgery, further signifying their relationship to the pathology. The panel of two plasma miRNAs, miR-122-3p, and miR-483-3p, could serve as a potential biomarker set (AUC = 0.84) for the ascending TAA. The miRNA-target enrichment analysis exposed TGF-β signaling pathway as sturdily affected by abnormally expressed miRNAs in the TAA tissue. Nearly half of TAA-specific miRNAs potentially regulate a key component in TGF-β signaling: TGF-β receptors, SMADs and KLF4. Indeed, using immunohistochemistry analysis we detected increased KLF4 expression in 27% of TAA cells compared to 10% of non-TAA cells. In addition, qRT-PCR demonstrated a significant upregulation of ALK1 mRNA expression in TAA tissues. Overall, these observations indicate that the alterations in miRNA expression are sex-dependent and play an essential role in TAA via TGF-β signaling.
Our study provides evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii) FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection.
Objective: Surgical management of infective endocarditis continues to be challenging and is associated with significant morbidity and mortality. The objective of our study was to determine the risk factors and conditions associated with poor early infective endocarditis surgical treatment outcomes—30-day postoperative mortality. Methods: A total of 124 patients who underwent surgery for infective endocarditis at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from January 2010 to December 2017 were retrospectively included in this study. The primary endpoints were 30-day postoperative mortality and identification of risk factors associated with it. Secondary endpoints were early postoperative outcomes and complication rates. Results: During the study period, 124 patients with infective endocarditis underwent cardiac surgery, presenting an overall 30-day postoperative mortality rate of 10.48%. Mean age was 58 ± 14.4 years with 95 (76.61%) males. Independent predictive factors of early mortality were age >63 years (odds ratio = 6.4, 95% confidence interval = 1.66-24.66, p = 0.003), body mass index >30 kg/m² (odds ratio = 7.74, 95% confidence interval = 2.20-27.27, p = 0.003), and ischemic heart disease (odds ratio, 6.6, 95% confidence interval = 1.62-26.90, p = 0.003), as well as intraoperative parameters—prolonged aortic cross-clamp >84.5 minutes (odds ratio = 3.79, 95% confidence interval = 1.10-13.08, p = 0.03) and cardiopulmonary bypass time >107.5 minutes (odds ratio = 10.0, 95% confidence interval = 1.26-79.58, p = 0.023). Staphylococcus aureus infection (odds ratio = 5.04, 95% confidence interval = 1.29-19.64, p = 0.012), infective endocarditis–related intracardiac complication such as paravalvular abscess detected by transesophageal echocardiography (odds ratio = 4.32, 95% confidence interval = 1.31-14.25, p = 0.01), and infective endocarditis complicated by septic or cardiogenic shock (odds ratio, 18.43, 95% confidence interval = 4.59-73.98, p = 0.001) were statistically significant factors for increased risk of 30-day postoperative mortality. Conclusion: Surgical treatment of infective endocarditis showed good results in our center. The independent predictors of 30-day postoperative mortality for patients who underwent cardiac surgery for infective endocarditis were age, body mass index, ischemic heart disease, prolonged aortic cross-clamp and cardiopulmonary bypass time, Staphylococcus aureus infection, paravalvular abscess, and septic or cardiogenic shock.
Transforming growth factor β1 (TGF- β1) is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- β1 levels are associated with Marfan syndrome (MFS) caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- β1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA) and in reference group subjects (n = 212). An initial screening of 212 reference individuals identified TGF- β1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- β1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1–25.3, and median 6.2 ng/ml, range 1.0–33.1, respectively). There is a significant association between TGF-β1 concentration and DPAA (OR 1.084, CI 1.027–1.144, p = 0.004) but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-β1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-β1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-β1 levels with an emphasis on preanalytical phase and the choice of sample.
Background and Objectives. Thoracic aortic aneurysm (TAA) is a silent disease characterised by aortic wall expansion and vascular smooth muscle cell (VSMC) dedifferentiation from contractile to synthetic phenotype. Long noncoding RNAs (lncRNAs) involved in VSMC phenotypic regulation could be considered as potential diagnostic indicators and therapeutic targets of TAA. In vitro studies show that lncRNAs CARMN, LUCAT1, MALAT1, and SMILR are associated with the VSMC phenotypic state. Our aim was to test if these lncRNAs are dysregulated during TAA formation in clinical patient samples. Materials and Methods. Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method. The Mann–Whitney U test was used to compare ΔCt values between the study groups. ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs. Results. We found significantly reduced CARMN (p=0.033) and LUCAT1 (p=0.009) expression in aortic tissue samples from TAA patients. Relative expression of MALAT1 (p=0.117) and SMILR (p=0.610) did not differ in aortic tissue between the TAA and non-TAA groups. Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients’ blood plasma compared to controls (p=0.018 and p=0.032, respectively). However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients’ blood plasma (AUC=0.654, 95%CI=0.534‐0.775, p=0.018). Conclusions. We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients. Decreased LUCAT1 expression in TAA patients’ blood plasma may have diagnostic potential in discriminating patients with TAA.
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