miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities.

Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.

The role of the female gender on mid-term outcome after coronary artery bypass grafting: a retrospective study.

Background: Data on female gender differences on clinical prognosis after coronary artery bypass grafting (CABG) are still controversial. We evaluated retrospectively the impact of women patients in comparison with men undergoing CABG on mid-term outcome. Methods: Between December 2014 and March 2022, 1,044 consecutive patients (162 females, 15.5%, 882 males, 84.5%) underwent isolated CABG. The mean follow-up was 40±27 (median 38) months. Logistic and Cox model analysis regressions were used to assess the risk of female gender and other variables, Kaplan-Meier estimates to assess survival rates. Results: Women did not have a significant higher operative mortality than men (3.09% vs. 1.93%; P=0.37). There was no difference in the use of left internal mammary artery (97.5% vs. 94.9%; P=0.85). Independent predictors of early mortality were emergency CABG (P<0.0001), percutaneous coronary intervention (PCI) within 30 days (P=0.0026), and higher EuroSCORE II (P=0.0155). At 7.5 years, actuarial survival was 87%±3.6% for female gender vs. 88%±1.9% in male gender (P=0.41), freedom from cardiac death 97%±1.8% vs. 96.6%±1.0% (P=0.6), freedom from major adverse cardiac events (MACE) 87%±6.2% vs. 89.7%±2.5% (P=0.96). Independent predictor of all-causes death and cardiac death was the advanced age (74 years in dead patients vs. 67 years in survivors) (P<0.0001). Female gender was not a predictor of either operative mortality (P=0.34) or worse mid-term outcome (P=0.41). Conclusions: Women undergoing CABG with the same surgical techniques currently adopted for men, do not appear to be associated with worse early prognosis. Freedom from late all-causes mortality, cardiac death and adverse cardiac events are comparable and equally satisfactory, highlighting the positive protective effect of CABG over time also in women.

CAR, mGPS and hs-mGPS: What is among them the best gero-biomarker for age-related diseases? And for what clinical application?

The identification of biomarkers linked to the onset, progression, and prevention of age-related diseases (ARD), in the era of personalized medicine, represents the best goal of geroscience. Geroscience has the fundamental role of exploring and identifying the biological mechanisms of aging to suggest interventions capable of stopping/delaying the many pathological conditions and disabilities related to age. Therefore, it has become its key priority, as well as that of clinical practice and research, based on identifying and validating a range of biomarkers, geromarkers, which can be used to diagnostic, prognostic, or predictive clinical purposes. Indeed, geromarkers have, the potential to predict ARD trajectories and facilitate targeted interventions to slow down the related disabilities. Here our attention is paid to the inflammatory indexes (CAR, mGPS, hs-mGPS) linked to the relationship between the plasma levels of two inflammatory analytes, the typical positive protein of the acute phase, and the negative one, i.e. c-reactive protein (CRP) and albumin, respectively. These indexes allow us to understand the magnitude of the two main mechanisms predicted to influence the aging process, including inflammation and immunosenescence, as well as the degree of ARD severity. Evidence on their relationship with ARD is widely reported and discussed, to understand which can represent the best ARD geromarker, and its clinical application.

miRNA-Driven Regulation of Endothelial-to-Mesenchymal Transition Differs among Thoracic Aortic Aneurysms.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

Early-Staged Carotid Artery Stenting Prior to Coronary Artery Bypass Grafting: Analysis of the Early and Mid-Term Results in Comparison with a Consecutive Cohort of Isolated Coronary Artery Surgery Patients.

AIM: The aim of the present study was to analyze retrospectively the results of patients who underwent early-staged, i.e., within 24-48 h, carotid artery stenting (e-s CAS) before coronary artery bypass grafting (CABG). METHODS: Between December 2014 and December 2022, 1046 consecutive patients underwent CABG; 31 of these patients (3%) were subjected to e-s CAS prior to CABG (e-s CAS + CABG group). Preoperative and intraoperative variables and early and mid-term results of the e-s CAS + CABG group were compared with those of patients who underwent isolated CABG (CABG group). RESULTS: As compared with the CABG group, the e-s CAS + CABG group showed a worse clinical risk profile due to higher Euroscore-2 values and incidence of obstructive pulmonary disease and bilateral carotid artery and peripheral artery diseases (p < 0.05, for all comparisons). The combined end point of operative mortality, periprocedural myocardial infarction, and stroke was 3.2% (0%/0%/3.2%) in the e-s CAS + CABG group vs. 5.9% (2.2%/2.8%/0.9%) in the CABG group (p > 0.5, for all measurements). At 5 years, actuarial survival was 74% ± 16% in the e-s CAS + CABG group vs. 93% ± 4.0% in the CABG group, freedom from cardiac death was 100% vs. 98% ± 1.0% (p = 0.6), and freedom from MACCEs was 85% ± 15% vs. 97% ± 2.5% (p > 0.1, for all comparisons). Independent predictors of all-causes death were advanced age at the operation (p < 0.0001), a lower value for left ventricular ejection fraction (p = 0.05), and a high Euroscore-2 (p = 0.04). CONCLUSIONS: CABG preceded by e-s CAS appears to be associated with satisfactory early outcomes while limiting the risk of myocardial infarction to a very short time interval between the two procedures. Freedom from late all-causes death, cardiac death, and MACCEs were comparable and equally satisfactory, underscoring the positive protective effects of CAS and CABG on the carotid and coronary territories over time.

Transcatheter aortic valve replacement in the management of aortic insufficiency secondary to left ventricular assist device implantation: a case report.

Background: Left ventricular assist device (LVAD) is considered either a destination therapy for patients with end-stage heart failure or heart transplantation bridging. LVAD implantation often causes aortic insufficiency (AI), which requires aortic valve repair. However, severe acute AI does not respond well to medication, and re-operation means higher risk to the patients; the most effective therapeutic strategies for LVAD-induced AI still need further exploration. In this report, we present the first described case of new-onset, severe LVAD-induced AI in China with a patient who underwent transcatheter aortic valve replacement (TAVR) and achieved significant improvement in functional capacity and symptoms with lower operation risk. Case Description: A 55-year-old male patient was diagnosed with dilated cardiomyopathy for 14 years. The effect of the medication gradually deteriorated, LVAD (HeartCon®) was implanted one year earlier. The patient complained of intermittent chest tightness for one week, which had been aggravated for two days before hospitalization. Echocardiographic findings revealed new-onset, severe LVAD-induced AI. TAVR was performed with a self-expandable stent-valve (TAV30, Vitaflow Liberty). Within minutes, the patient recovered with rapid disappearance of chest tightness and stable vital signs. Before discharge, the position of the artificial valve was fixed without incomplete closure nor thrombus attachment, yielding a left ventricular ejection fraction (LVEF) of 35%. The patient was hospitalized for 38 days, and followed up with outpatient treatment, the condition was stable until 19 June 2023. Conclusions: TAVR could be an effective, safe, and less invasive means of restoring ejection fraction for patients with a LVAD who develop severe AI.