Browsing by Author "Akar, Ahmet Ruchan"
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Item Increased free Zn2+ correlates induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn2+-transporters in heart failure(WILEY, 2018-01-01) Olgar, Yusuf; Durak, Aysegul; Tuncay, Erkan; Bitirim, Ceylan Verda; Ozcinar, Evren; Inan, Mustafa Bahadir; Tokcaer-Keskin, Zeynep; Akcali, Kamil Can; Akar, Ahmet Ruchan; Turan, BelmaZn2+-homoeostasis including free Zn2+ ({[}Zn2+](i)) is regulated through Zn2+-transporters and their comprehensive understanding may be important due to their contributions to cardiac dysfunction. Herein, we aimed to examine a possible role of Zn2+-transporters in the development of heart failure (HF) via induction of ER stress. We first showed localizations of ZIP8, ZIP14 and ZnT8 to both sarcolemma and S(E)R in ventricular cardiomyocytes (H9c2 cells) using confocal together with calculated Pearson's coefficients. The expressions of ZIP14 and ZnT8 were significantly increased with decreased ZIP8 level in HF. Moreover, {[}Zn2+](i) was significantly high in doxorubicin-treated H9c2 cells compared to their controls. We found elevated levels of ER stress markers, GRP78 and CHOP/Gadd153, confirming the existence of ER stress. Furthermore, we measured markedly increased total PKC and PKC alpha expression and PKC alpha-phosphorylation in HF. A PKC inhibition induced significant decrease in expressions of these ER stress markers compared to controls. Interestingly, direct increase in {[}Zn2+](i) using zinc-ionophore induced significant increase in these markers. On the other hand, when we induced ER stress directly with tunicamycin, we could not observe any effect on expression levels of these Zn2+ transporters. Additionally, increased {[}Zn2+](i) could induce marked activation of PKC alpha. Moreover, we observed marked decrease in {[}Zn2+](i) under PKC inhibition in H9c2 cells. Overall, our present data suggest possible role of Zn2+ transporters on an intersection pathway with increased {[}Zn2+](i) and PKC alpha activation and induction of HF, most probably via development of ER stress. Therefore, our present data provide novel information how a well-controlled {[}Zn2+](i) via Zn2+ transporters and PKC alpha can be important therapeutic approach in prevention/treatment of HF.Item Raising the bar to ultradisciplinary collaborations in management of chronic thromboembolic pulmonary hypertension(BAYCINAR MEDICAL PUBL-BAYCINAR TIBBI YAYINCILIK, 2021-01-01) Akay, Tankut; Kaymaz, Cihangir; Akar, Ahmet Ruchan; Orhan, Gokcen; Yanartas, Mehmed; Gultekin, Bahadir; Sirlak, Mustafa; Kervan, Umit; Tas, Serpil Gezer; Bicer, Murat; Yagdi, Tahir; Ispir, Selim; Dogan, RizaChronic thromboembolic pulmonary hypertension is an underdiagnosed and potentially fatal subgroup of pulmonary hypertension, if left untreated. Clinical signs include exertional dyspnea and non-specific symptoms. Diagnosis requires multimodality imaging and heart catheterization. Pulmonary endarterectomy, an open heart surgery, is the gold standard treatment of choice in selected patients in specialized centers. Targeted medical therapy and balloon pulmonary angioplasty can be effective in high-risk patients with significant comorbidities, distal pulmonary vascular obstructions, or recurrent/persistent pulmonary hypertension after pulmonary endarterectomy. Currently, there is a limited number of data regarding novel coronavirus-2019 infection in patients with chronic thromboembolic pulmonary hypertension and the changing spectrum of the disease during the pandemic. Challenging times during this outbreak due to healthcare crisis and relatively higher case-fatality rates require convergenceItem Validation of the EuroSCORE risk models in Turkish adult cardiac surgical population(OXFORD UNIV PRESS INC, 2011-01-01) Akar, Ahmet Ruchan; Kurtcephe, Murat; Sener, Erol; Alhan, Cem; Durdu, Serkan; Kunt, Ayse Gul; Guvenir, Halil Altay; Cardiovasc, Working Grp Turkish SocObjective: The aim of this study was to validate additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) models on Turkish adult cardiac surgical population. Methods: TurkoSCORE project involves a reliable web-based database to build up Turkish risk stratification models. Current patient population consisted of 9443 adult patients who underwent cardiac surgery between 2005 and 2010. However, the additive and logistic EuroSCORE models were applied to only 8018 patients whose EuroSCORE determinants were complete. Observed and predicted mortalities were compared for low-, medium-, and high-risk groups. Results: The mean patient age was 59.5 years (+/- 12.1 years) at the time of surgery, and 28.6\% were female. There were significant differences (all p < 0.001) in the prevalence of recent myocardial infarction (23.5\% vs 9.7\%), moderate left ventricular function (29.9\% vs 25.6\%), unstable angina (9.8\% vs 8.0\%), chronic pulmonary disease (13.4\% vs 3.9\%), active endocarditis (3.2\% vs 1.1\%), critical preoperative state (9.0\% vs 4.1\%), surgery on thoracic aorta (3.7\% vs 2.4\%), extracardiac arteriopathy (8.6\% vs 11.3\%), previous cardiac surgery (4.1\% vs 7.3\%), and other than isolated coronary artery bypass graft (CABG