Anatolian Journal of Cardiology最新文献

Background: A primary factor in the pathogenesis of aging is oxidative stress, with cardiac inflammation and fibrosis being contributed to by increased oxidative stress as organisms age. Oxidative stress enhances the cardiac fibrotic signaling pathway, with reactive oxygen species inducing cardiac fibrosis through increased expression of the profibrotic factor transforming growth factor-beta 1 (TGF-β1). Furthermore, Wnt/β-catenin signaling pathway is implicated in interstitial fibrosis, which is associated with TGF-β. Sirtuin 2 (SIRT2) is expressed in heart tissue, with protective effects in pathological cardiac hypertrophy. We aimed to investigate the mechanisms of cardiac fibrosis in D-Galactose (D-Gal)-induced accelerated aging, focusing on TGF-β1, β-catenin, and SIRT2.

Methods: A total of 30 young male Sprague-Dawley rats were randomly divided into 4 groups: control group, D-Gal group, D-Gal + 4% dimethyl sulfoxide (DMSO) group, and D-Gal + the SIRT2 inhibitor (AGK2) group. After 10 weeks, the rats were sacrificed, and their hearts were removed. SIRT2 expression levels were measured by western blot and gene expression levels of TGF-β1 and β-catenin by quantitative real-time polymerase chain reaction.

Results: Transforming growth factor-beta 1 (TGF-β1) mRNA expression in heart tissue was higher in the D-Gal group compared to all other groups. β-catenin mRNA expression was higher in the D-Gal group than in the D-Gal + AGK2 group. SIRT2 protein expression was higher in the D-Gal + DMSO group compared to the control group. Sirtuin 2 expression was lower in the D-Gal + AGK2 group compared to the D-Gal and D-Gal + DMSO groups.

Conclusion: Sirtuin 2 inhibition attenuates fibrosis, as evidenced by the downregulation of TGF-β1 and β-catenin. Thus, targeting SIRT2 may represent a potential therapeutic strategy for diseases characterized by cardiac fibrosis in the future.

Background: Type 2 diabetes mellitus (T2DM) patients with small-diameter stents (SDS), that are equal to or less than 2.5 mm in diameter, face increased risks of restenosis and complications. This study aimed to evaluate the 1-year follow-up to assess the rate of major adverse cardiac events (MACE) and bleeding risk between ticagrelor and clopidogrel in T2DM patients after SDS implantation.

Methods: The study was a single-center, prospective controlled registry trial, which included 332 T2DM patients who underwent percutaneous coronary intervention with SDS implantation. Follow-up was conducted for 1 year.

Results: Following propensity score matching, the 1-year analysis revealed no significant difference in the risk of the composite MACE between clopidogrel and ticagrelor groups (P = .295). Male gender, history of ischemic heart disease, ejection fraction (EF), coronary lesion type, and chronic kidney disease (CKD) were identified as potential predictors for the composite endpoint. In a subanalysis of CKD patients, the 12-month rates of composites of cardiac death (CD), myocardial infarction (MI), stroke, and target vessel revascularization (TVR) were lower in the ticagrelor group than in the clopidogrel group (P = .024). However, the ticagrelor group was associated with a higher rate of bleeding compared to the clopidogrel group (20% vs. 9%) (P = .041).

Conclusion: Our study demonstrated that ticagrelor did not show improvement in the composite of CD, MI, stroke, TVR, or the risk of bleeding events defined by the BARC criteria in patients with T2DM and SDS compared with clopidogrel emphasizing the importance of individualized treatment decisions based on patient characteristics. However, the results may not be representative of the entire population.

Background: There is increasing evidence that thrombomodulin (THBD) polymorphisms, along with inflammatory markers [i.e., C-reactive protein (CRP), fibrinogen, albumin], may increase the risk of acute myocardial infarction (AMI). The aim of the study was to investigate the role of the THBD -33G>A polymorphism (rs1042579) as a marker of AMI risk and to correlate it with serum levels of inflammatory markers.

Methods: Case-control study of 277 AMI patients and 329 healthy controls. A binary logistic regression analysis was performed to evaluate the association between the parameters studied and AMI risk.

Results: The frequencies of genotypes AA, GA, and GG of the THBD -33G>A polymorphism were 31.4%, 45.5%, and 23.1% in patients and 21.6%, 44.1%, and 34.3% in controls. A significant association was found between the AA genotype of the THBD -33G>A polymorphism (AA: OR = 2.011, 95% CI 1.561-3.074, P < .001) or A allele (A: OR = 1.725, 95% CI 1.493-2.510, P < .001) and AMI risk. A backward stepwise logistic regression method combining AMI status as the dependent variable and conventional risk factors (age, smoking, arterial hypertension (HTA), diabetes, dyslipidemia, CRP, albumin, fibrinogen, serum angiotensin converting enzyme (ACE) activity, serum malondialdehyde, conjugated dienes, glutathione peroxidase, cardiac troponin-I (cTnI) and THBD AA genotype) as independent variables showed that the most predictive risk factors for AMI were smoking, HTA, albumin, fibrinogen, CRP, ACE activity, cTnI, and the THBD AA-genotype with odds ratios of 2.942, 2.203, 2.352, 1.323, 1.652, 1.014, 2.105, and 3.781 respectively. The AA genotype was associated with increased diastolic blood pressure, CRP, ACE activity, and albumin levels.

Conclusions: The study shows that the THBD -33G>A polymorphism should be included in the stratification of AMI risk.

Background: The precise etiology of hypoplasia of the posterior mitral valve leaflet (PMVL) remains incompletely elucidated; however, it has been hypothesized to stem from genetic mutations occurring during fetal development. Herein, we present the anatomical characteristics of the mitral valve and associated cardiac pathologies in patients with hypoplastic PMVL.

Methods: This single-center retrospective study involved patients who presented between 2015 and 2021 at a tertiary healthcare facility. Among the cohort, 44 individuals had hypoplastic PMVL and were divided into 2 groups: those with severe mitral regurgitation (MR) and those with non-severe MR.

Results: Among the patients, 11 (25%) had severe MR. The median lengths for the PMVL was 5 mm (5-6). Moreover, 10 patients had concomitant muscular formation. We found that 13 patients had bicuspid aortic valve (BAV), while the second most common concomitant cardiac congenital pathology was secundum atrial septal defect (ASD) in 7 patients. The anterior mitral leaflet (AML) length (P = .007), AML prolapse (P < .001), and A2P2 distance (P = .008) were higher in the group with severe MR. In addition, muscular formation was more common in patients with hypoplastic PMVL with severe MR (P < .001).

Conclusion: Hypoplastic PMVL is a rare but significant anomaly that causes MR. While it can coexist with numerous congenital conditions, the most frequent associations include BAV and, secondly, ASD. Severe MR is particularly observed in cases accompanied by dilated mitral annulus, AML prolapse, and muscular formation.

Background: Cardiac fibrosis, a key contributor to heart failure, is driven by the activation of cardiac fibroblasts (CFs), often induced by angiotensin II (Ang II). Relaxin, a peptide hormone, has been reported to counteract fibrotic processes. This study aims to investigate the antifibrotic effects of relaxin on Ang II-induced CF activation, with a focus on the involvement of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway.

Methods: Primary CFs were isolated and treated with Ang II to induce fibrotic activation. Relaxin was used to assess its antifibrotic effects. Inhibitors of the NO/cGMP pathway, NG-nitro-L-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor) and 1H-(1 ,2,4) -Oxadiazolo-(4, 3-a) quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor), were co-administered to examine their effects on relaxin-mediated inhibition. Proliferation and migration were assessed using 5-Ethynyl-2'-de oxyur idine incorporation and Transwell assays. Western blot analysis was conducted to measure the expression of alpha-smooth muscle actin (α-SMA), collagen I, and collagen III, key markers of fibroblast activation. Nitric oxide, cGMP, total nitric oxide synthase (TNOS), and inducible nitric oxide synthase (iNOS) levels were measured in the culture media.

Results: Ang II significantly increased CF proliferation, migration, and the expression of fibrosis markers α-SMA, collagen I, and collagen III. Relaxin treatment markedly reduced these effects. Inhibition of the NO/cGMP pathway by L-NAME or ODQ partially reversed relaxin's suppressive effects on CF proliferation and migration. Relaxin restored Ang II-induced reductions in NO, cGMP, and TNOS levels, while iNOS levels remained largely unchanged, except for a reduction in the L-NAME group.

Conclusion: Relaxin attenuates Ang II-induced cardiac fibroblast activation and fibrosis primarily through the NO/cGMP signaling pathway.