The limited regenerative capacity of the injured myocardium leads to remodeling and often heart failure. Novel therapeutic approaches are essential. Induced pluripotent stem cells (iPSC) ...differentiated into cardiomyocytes are a potential future therapeutics. We hypothesized that organ-specific reprogramed fibroblasts may serve an advantageous source for future cardiomyocytes. Moreover, exosomes secreted from those cells may have a beneficial effect on cardiac differentiation and/or function. We compared RNA from different sources of human iPSC using chip gene expression. Protein expression was evaluated as well as exosome micro-RNA levels and their impact on embryoid bodies (EBs) differentiation. Statistical analysis identified 51 genes that were altered (
≤ 0.05), and confirmed in the protein level, cardiac fibroblasts-iPSCs (CF-iPSCs) vs. dermal fibroblasts-iPSCs (DF-iPSCs). Several miRs were altered especially miR22, a key regulator of cardiac hypertrophy and remodeling. Lower expression of miR22 in CF-iPSCs vs. DF-iPSCs was observed. EBs treated with these exosomes exhibited more beating EBs
= 0.05. vs. control. We identify CF-iPSC and its exosomes as a potential source for cardiac recovery induction. The decrease in miR22 level points out that our CF-iPSC-exosomes are naïve of congestive heart cell memory, making them a potential biological source for future therapy for the injured heart.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aims
To assess the short‐term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective ...single‐centre cohort study of HTx recipients who received a two‐dose SARS‐CoV‐2 mRNA vaccine (BNT162b2, Pfizer‐BioNTech).
Methods and results
Whole blood for anti‐spike IgG (S‐IgG) antibodies was drawn at days 21–26 and at days 35–40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 interquartile range (IQR) 44–69 years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6–14) years. Only 15% of HTx recipients demonstrated the presence of positive S‐IgG antibody titres in response to the first vaccine dose GMT 90 (IQR 54–229) AU/mL. Overall, 49% of HTx recipients induced S‐IgG antibodies in response to either the first or the full two‐dose vaccine schedule GMT 426 (IQR 106–884) AU/mL. Older age 68 (IQR 59–70) years vs. 46 (IQR 34–63) years, P = 0.034 and anti‐metabolite‐based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non‐responders to the first vaccine dose became S‐IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S‐IgG antibodies following SARS‐CoV‐2 two‐dose vaccine.
Conclusions
The generally achieved protection from SARS‐CoV‐2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial showed that the SYNTAX score (SS) is a useful tool for customizing revascularization treatment for ...patients with multivessel coronary disease. In the past decade, the Clinical SS (CSS) has emerged as a comprehensive tool. This novel tool considers the SS as well as patient clinical parameters such as age, creatinine clearance, and ejection fraction, which were shown to be relevant for patient prognosis. Thus, in the current work we set out to compare the survival predictive values of the SS versus the CSS and their future application in real-world implementation of the revascularization guidelines.
This study was a subanalysis of data collected in a prospective national registry in Israel that enrolled consecutive patients with left main and/or 2- to 3-vessel coronary artery disease involving the proximal or mid-left anterior descending artery; the MULTI-vessel Coronary Artery Disease (MULTICAD). The revascularization method was chosen by the physicians taking care of the patients at each hospital and the patients were followed for 5 years. Patients were categorized according to their SS, the CSS, and their revascularization method (primary coronary intervention PCI vs coronary artery bypass grafting CABG) and patient survival were compared.
A total of 585 patients were enrolled in the study and were followed for 5 years. The median CSS was 27, with 288 patients showing a CSS ≥27, with a mean CSS of 47.85 and a mean SS of 29.05. At 3 and 5 years post-treatment, the CSS ≥27 group had a lower survival probability, CSS ≥27 was associated with a lower survival probability among patients who underwent PCI compared with those who underwent CABG. More specifically, the high-CSS CABG group had a 5-year mortality rate of 16.8%, whereas the high-CSS PCI group had a 5-year mortality rate of 32.2%. In a comparison of SS with CSS for the 5-year mortality outcome prediction, CSS was superior to SS with a higher area under the curve.
This prospective registry of real-world revascularization strategies in patients with multivessel disease showed that CSS is a better predictive tool of postrevascularization survival than SS. Moreover, it showed that surgical revascularization in patients with CSS ≥27 is associated with better all-cause mortality outcome after CABG as compared with after PCI. This attests to the need for a score that considers clinical parameters in a real-world scenario.
This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart ...tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8, and PSMB9 (proteasome β-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Port-Access mitral valve surgery has been around since 1995; and many variations upon the technique have been developed. Since 1996 we have performed more than 2,500 port-Access mitral valve ...surgeries, and thus gained a substantial experience. The purpose of this document is to describe the current status of port access mitral surgery at one institution, and to share the “know how” and life lessons behind the patient selection and conduct of the operation to accomplish results similar to those achieved from sternotomy mitral valve surgery. While port access started in larger institutions, it can be performed in small centers with the proper guidance of the pearls and pitfalls of this operation, given to young surgeons regarding the right way to start a program.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting ...enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice.
Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested.
ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment.
Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Female lung transplant recipients (LTRs) of reproductive age are increasingly considering pregnancy due to advances in post‐transplant management and improved survival. We report our ...experience with pregnancy in LTRs, with an emphasis on two or more successful full‐term pregnancies in individual transplant recipients.
Methods
We conducted a retrospective analysis of pregnancies in LTRs at our transplant center and collected maternal and fetal outcomes.
Results
In our patient cohort, eight female LTRs conceived a total of 17 pregnancies, resulting in 13 newborns, 12 at full term, and 11 with a birth weight > 2.5 kg. Three of the LTRs had two or more successful full‐term pregnancies. LTRs required a significant tacrolimus dose increase to maintain target trough levels during pregnancy. Six recipients are currently clinically stable and active, three with lung function comparable to pre‐pregnancy values, and three with evidence of chronic lung allograft dysfunction (CLAD), but stable lung function. Two of the eight LTRs died subsequent to childbirth secondary to chronic respiratory failure due to CLAD, at a mean of 11 years post‐transplantation and a mean of 4.5 years after childbirth.
Conclusion
Pregnancy following lung transplantation is feasible and can be achieved with acceptable maternal and newborn outcomes. Importantly, LTRs can successfully have two or more full‐term pregnancies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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