{"title":"CD4+CD25+Treg Cells Prolong the Survival Time of Heart Allograft Via Induction Lymphocyte Apoptosis and Modulation the Ratio of T Cell Subsets","authors":"Jinguo Zhu, L. Xiong","doi":"10.26502/fccm.92920245","DOIUrl":"https://doi.org/10.26502/fccm.92920245","url":null,"abstract":"Background: CD4CD25regulatory T cells (CD4CD25 Treg cells) play major roles in immune regulation. Previous studies showed CD4CD25 Treg cells can maintain peripheral immune tolerance and increase the survival time of transplanted organs. However, the biological characteristics and the functional roles of these CD4CD25 Treg cells in transplantation tolerance remain unknown. The current study was conducted to observe the effect of CD4CD25 Treg cells on heart allograft in rats and to investigate the underlying mechanism of the CD4CD25 Treg cells. Methods: 5 x 10 spleen cells of SD rats were inoculated into the thymus gland of Wistar rats. The level of CD4CD25 Treg cells was examined by the flow cytometry method, and the biological activity of CD4CD25 Treg cells was detected by the H-TdR method. Hearts were transplanted from SD rats (donors) to Wistar rats (recipients) and the animals were assigned into four groups: HT, HT+Ii,HT+Treg, HT+Treg+Ii. At various time points after the transplantation, the transplanted hearts were collected and histologically examined. The rate of lymphocyte Cardiol Cardiovasc Med 2022; 6 (2): 71-82 DOI: 10.26502/fccm.92920245 Cardiology and Cardiovascular Medicine Vol. 6 No. 2 – April 2022. [ISSN 2572-9292] 72 apoptosis and T cell subsets in the peripheral blood of Wistar rats were analyzed with flow cytometry. Results: The CD4+CD25+ Treg cells in Wistar rats were sharply increased, and these CD4CD25 Treg cells significantly extended the survival time: The mean survival time of the transplanted hearts was 8.1 ± 1.2 days, 35.7 ± 4.7 days,53.7 ± 6.2 days, 75.7 ± 11.3 days in the group of HT, HT+Ii, HT+Treg, or HT+Ii+Treg, respectively (n = 12-14/group). Among them, the survival time between HT and HT+Treg or between HT and HT+Treg+Ii was significantly different (p<0.001). Also, we found that CD4CD25 Treg cells improved the pathological changes of the transplanted hearts, increased the rate of lymphocyte apoptosis, upregulated CD3CD8T cells, and suppressed CD3CD4 T cells. Conclusions: CD4CD25 Treg cells appear to be able to induce tolerance in heart transplantation. This is largely due to the CD4CD25 Treg cellsdependent alteration of the ratio of T cell subsets and the induction of lymphocyte apoptosis.","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69346210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ventricular Hyper-Excitability Revealing Cardiac and Mediastino-Pulmonary Sarcoidosis","authors":"H. Mokhlis","doi":"10.26502/fccm.92920292","DOIUrl":"https://doi.org/10.26502/fccm.92920292","url":null,"abstract":"Sarcoidosis, also known as Besnier-Boeck-Schaumann disease, first described in 1877 [1], is a systemic granulomatous disease that affects multiple organs (nervous system, heart, liver and kidneys.. ....), but mainly affects the lungs and lymph glands. Sarcoidosis has no known cause, and it can affect a wide range of people and present a real diagnostic challenge. Cardiac sarcoidosis can manifest as complete heart block, ventricular arrhythmias, congestive heart failure, pulmonary hypertension, and ventricular aneurysms.","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69346780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Avinash Mani, V. Ojha, Pradip Kumar Sinha, Jayanta Saha
{"title":"Evaluation of D-Dimer Levels in Various Subgroups of Atrial Fibrillation: Role in Risk Stratification","authors":"Avinash Mani, V. Ojha, Pradip Kumar Sinha, Jayanta Saha","doi":"10.26502/fccm.92920300","DOIUrl":"https://doi.org/10.26502/fccm.92920300","url":null,"abstract":"Results: 70 patients with AF were studied over a one-year period. Mean age of study population was 53 years. Valvular AF was the most common etiology(30%) noted followed by non-ischemic cardiomyopathy (NICM) (14.2%). About half of study population had history of heart failure whereas thromboembolism(TE) was noted in 15.7%. 72.8% patients had elevated D-dimer levels in the cohort. D-dimer levels were significantly higher in valvular AF(1.2 μg/ml) and NICM patients(1.4 μg/ml) (p=0.005). Higher D-dimer levels were noted in those with heart failure (HF) events (p=0.016). D-dimer levels were shown to accurately detect prior HF/ TE events with levels of 1.1 μg/ml and higher having a sensitivity and specificity of 59.1% and 81%, respectively (AUC 0.727).","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69347280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina J Codden, Amy Larson, Junya Awata, Gayani Perera, Michael T Chin
{"title":"Single Nucleus RNA-sequencing Reveals Altered Intercellular Communication and Dendritic Cell Activation in Nonobstructive Hypertrophic Cardiomyopathy.","authors":"Christina J Codden, Amy Larson, Junya Awata, Gayani Perera, Michael T Chin","doi":"10.26502/fccm.92920277","DOIUrl":"https://doi.org/10.26502/fccm.92920277","url":null,"abstract":"<p><p>End stage, nonobstructive hypertrophic cardiomyopathy (HCM) is an intractable condition with no disease-specific therapies. To gain insights into the pathogenesis of nonobstructive HCM, we performed single nucleus RNA-sequencing (snRNA-seq) on human HCM hearts explanted at the time of cardiac transplantation and organ donor hearts serving as controls. Differential gene expression analysis revealed 64 differentially expressed genes linked to specific cell types and molecular functions. Analysis of ligand-receptor pair gene expression to delineate potential intercellular communication revealed significant reductions in expressed ligand-receptor pairs likely affecting the extracellular matrix, growth factor binding, peptidase regulator activity, platelet-derived growth factor binding and protease binding in the HCM tissue. Changes in Integrin-β1 receptor expression were responsible for many observed changes related to extracellular matrix interactions, by increasing in dendritic, smooth muscle and pericyte cells while decreasing in endothelial and fibroblast cells, suggesting potential mechanisms for fibrosis and microvascular disease in HCM and a potential role for dendritic cells. In contrast, there was an increase in ligand-receptor pair expression associated with adenylate cyclase binding, calcium channel molecular functions, channel inhibitor activity, ion channel inhibitor activity, phosphatase activator activity, protein kinase activator activity and titin binding, suggesting important shifts in various signaling cascades in nonobstructive, end stage HCM.</p>","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":" ","pages":"398-415"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33509131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Hashemi, Cachet Magdolna Wenziger, Tran Do, Arpan A. Patel, J. Pisegna, T. Ganz, M. Budoff, J. Gornbein, David A. Elashoff, E. Streja
{"title":"Association of Increased Risk of Atherosclerotic Cardiovascular (ASCVD) Event in Chronic Liver Disease Patients with and without Cirrhosis","authors":"L. Hashemi, Cachet Magdolna Wenziger, Tran Do, Arpan A. Patel, J. Pisegna, T. Ganz, M. Budoff, J. Gornbein, David A. Elashoff, E. Streja","doi":"10.26502/fccm.92920242","DOIUrl":"https://doi.org/10.26502/fccm.92920242","url":null,"abstract":"Background: An area of debate in modern medicine is whether there is an association between cirrhosis and Atherosclerotic Cardiovascular Disease (ASCVD). To address this we conducted a retrospective cohort study composed of the 486,887 US Veterans with liver disease over the period of January 2000 to December 2019 to ascertain whether there is an association between cirrhosis and ASCVD. We further divided the cohort based on a diagnosis of cirrhosis. Cox-Regression, negative binomial and competing risk models were used to investigate the time interval between the first and recurrent ASCVD hospitalization with mortality as a competing event risk. The mean± SD age of the cohort was 58 11 years, 4.6% were female, 63% White, 21% Black. 58% of the cohort had liver disease without a diagnosis of cirrhosis. The incidence of ASCVD hospitalization was much higher in liver patients with diagnosis of cirrhosis (11% vs 6%, p value<0.001). In a non-adjusted model with cirrhosis as the exposure the rate of first ASCVD hospitalization was 1.5 times higher than liver disease in patients without cirrhosis (HR: 1.49 (95%CI: 1.471.50), p <0.001). In a fully adjusted model, the risk was attenuated but remained statistically significant (HR: 1.03 (95% CI:1.02-1.04, p <0.001)). The mean number of ASCVD hospitalizations in a count model was 30% lower in the cirrhosis group (mean count ratio 0.70 (95% CI: 0.68-.072)), due to higher competing risk of all-cause mortality with ASCVD events (0.77 (0.73-0.81)). Conclusion: We demonstrate in this retrospective cohort study that as liver disease progresses to cirrhosis, the risk of ASCVD events increases. We hypothesize that the pro-inflammatory states of liver disease could be a viable explanation for the increased risk of ASCVD events in cirrhosis patients. Further translational studies are needed to confirm this hypothesis.","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69346139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute Ischemic Stroke Patients for Alteplase or Medical Care Alone or Intervention with/without Alteplase in Palestine (AIS-AMI Palestine)","authors":"M. Habib, Majed Alshounat, Mohammed Salama","doi":"10.26502/fccm.92920294","DOIUrl":"https://doi.org/10.26502/fccm.92920294","url":null,"abstract":"","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69346783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filippo Naso, Antonio Maria Calafiore, Mario Gaudino, Peter Zilla, Axel Haverich, Andrea Colli, Robert John Melder, Alessandro Gandaglia
{"title":"Polyphenols could be Effective in Exerting a Disinfectant-Like Action on Bioprosthetic Heart Valves, Counteracting Bacterial Adhesiveness.","authors":"Filippo Naso, Antonio Maria Calafiore, Mario Gaudino, Peter Zilla, Axel Haverich, Andrea Colli, Robert John Melder, Alessandro Gandaglia","doi":"10.26502/fccm.92920287","DOIUrl":"https://doi.org/10.26502/fccm.92920287","url":null,"abstract":"<p><strong>Background: </strong>The incidence of infective endocarditis in patients with bioprosthetic heart valves is over 100 times that of the general population with <i>S. aureus</i> recognized as the causative organism in approximately 1/3 of cases. In this study, (1) the microbicidal and virucidal effect of a polyphenolic solution was carefully evaluated. The same solution was then adopted for the treatment of a commercial bioprosthetic heart valve model for (2) the assessment of inhibition of <i>S. aureus</i> adhesiveness.</p><p><strong>Methods: </strong>(1) the viability of 9 microorganisms strains (colony-forming units) and the infectivity degree of 3 viral strains (cellular infection capacity) were evaluated after suspension in the polyphenolic solution. (2) Leaflets from a treated and untreated commercial surgical valve model were incubated with a known concentration of <i>S. aureus</i>. After incubation, the leaflets were homogenized and placed in specific culture media to quantify the bacterial load.</p><p><strong>Results: </strong>(1) The polyphenolic solution proved to be effective in eliminating microorganisms strains guaranteeing the killing of at least 99.9%. The effectiveness is particularly relevant against <i>M. chelonae</i> (99.999%). (2) The polyphenol-based treatment resulted in the inhibition of the S. aureus adhesiveness by 96% concerning untreated samples.</p><p><strong>Conclusions: </strong>The data suggest an interesting protective effect against infections and bacterial adhesiveness by a polyphenolic-based solution. Further studies will plan to extend the panel of microorganisms for the evaluation of the anti-adhesive effect; however, the use of optimized polyphenolic blends could lead to the development of new treatments capable to make transcatheter-valve substitutes more resistant to infection.</p>","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":" ","pages":"487-492"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9601395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40652304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan Enrique Puche García, Marta Iturregui Guevara, Etelvino Silva García, Raquel Campuzano Ruiz, Rafael Vázquez García
{"title":"Impact of Coronavirus-19 Pandemic and Lockdown on Admissions for Ischemic Heart Disease.","authors":"Juan Enrique Puche García, Marta Iturregui Guevara, Etelvino Silva García, Raquel Campuzano Ruiz, Rafael Vázquez García","doi":"10.26502/fccm.92920270","DOIUrl":"https://doi.org/10.26502/fccm.92920270","url":null,"abstract":"<p><strong>Background: </strong>In early 2020, the SARS-CoV-2 pandemic caused an unprecedented overload for the health service. A decrease in admissions for Acute Coronary Syndrome (ACS) was reported during lockdown, although many aspects remain to be clarified. The main objective of this study was to evaluate the impact of the pandemic and of lockdown itself in this area.</p><p><strong>Methods: </strong>We performed a retrospective observational study based on data from patients who visited the emergency department of a tertiary hospital with chest pain during 2018-2020, as well as those who were admitted for ACS. Personal details, date of admission, additional test results (laboratory and echocardiography), and therapy were recorded. Patients were divided into 3 groups: preCOVID (n=1,301), lockdown (n=45), and postlockdown (n=343).</p><p><strong>Results: </strong>Fewer visits to the emergency department for chest pain and admissions for ACS were recorded during lockdown (48.6% and 51.1% respectively, p<0.05). Patients who were admitted during lockdown were characterized by poorer control of cardiovascular risk factors, visited later (more evolving infarctions: 2.7% vs. 14.3%, p<0.05), experienced more echocardiographic complications during admission, and had more than 3-fold mortality rates (both in-hospital and postdischarge).</p><p><strong>Conclusion: </strong>The COVID-19 pandemic and lockdown itself had a negative effect on ischemic heart disease beyond SARS-CoV-2 infection.</p>","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"6 4","pages":"353-363"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vikrant Rai, Mohamed M Radwan, Sunil Nooti, Finosh G Thankam, Harbinder Singh, Devendra K Agrawal
{"title":"TLR-4 Inhibition Attenuates Inflammation, Thrombosis, and Stenosis in Arteriovenous Fistula in Yucatan Miniswine.","authors":"Vikrant Rai, Mohamed M Radwan, Sunil Nooti, Finosh G Thankam, Harbinder Singh, Devendra K Agrawal","doi":"10.26502/fccm.92920280","DOIUrl":"https://doi.org/10.26502/fccm.92920280","url":null,"abstract":"<p><p>Arteriovenous fistula (AVF) is the preferred vascular access in hemodialysis patients; however, it is afflicted with a high failure rate. Chronic inflammation, excessive neointimal hyperplasia (NIH), vessel stenosis, early thrombosis, and failure of outward remodeling are the major causes of AVF maturation failure. Inflammatory mediator toll-like receptor (TLR)-4 plays a critical role in NIH, arterial thrombosis, and stenosis. We investigated the effect of TLR-4 inhibition on early thrombosis. Yucatan miniswine were used to create AVF involving femoral artery and femoral vein and treated with TLR-4 inhibitor TAK-242 with ethanol as the vehicle. The vessels were assessed after 12 weeks using histomorphometry, immunostaining, ultrasound, angiography, and optical coherence tomography. Inhibition of TLR-4 attenuated inflammation and early thrombosis in 50% of animals, and blood flow was present through AVF in 25% of animals. Thus, targeting TLR-4 to attenuate inflammation and early thrombosis might be a therapeutic approach to keep AVF patent and maintain blood flow through the outflow vein.</p>","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"6 5","pages":"432-450"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33478340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Finosh G Thankam, Mohamed Radwan, Angelo Keklikian, Manreet Atwal, Taj Rai, Devendra K Agrawal
{"title":"Fluoroscopy Guided Minimally Invasive Swine Model of Myocardial Infarction by Left Coronary Artery Occlusion for Regenerative Cardiology.","authors":"Finosh G Thankam, Mohamed Radwan, Angelo Keklikian, Manreet Atwal, Taj Rai, Devendra K Agrawal","doi":"10.26502/fccm.92920284","DOIUrl":"https://doi.org/10.26502/fccm.92920284","url":null,"abstract":"<p><strong>Background: </strong>Despite the recent advancements in the cardiac regenerative technologies, the lack of an ideal translationally relevant experimental model simulating the clinical setting of acute myocardial infarction (MI) hurdles the success of cardiac regenerative strategies.</p><p><strong>Methods: </strong>We developed a modified minimally invasive acute MI model in Yucatan miniswine by catheter-driven controlled occlusion of LCX branches for regenerative cardiology. Using a balloon catheter in three pigs, the angiography guided occlusion of LCX for 10-15 minutes resulted in MI induction which was confirmed by the pathological ECG changes compared to the baseline control.</p><p><strong>Results: </strong>Ejection fraction was considerably decreased post-procedure compared to the baseline. Importantly, the highly sensitive MI biomarker Troponin I was significantly increased in post-MI and follow-up groups along with LDH and CCK than the baseline control. The postmortem infarct zone tissue displayed the classical features of MI including ECM disorganization, hypertrophy, inflammation, and angiogenesis confirming the MI at the tissue level.</p><p><strong>Conclusions: </strong>The present model possesses the advantage of minimal mortality, simulating the pathological features of clinical MI and the suitability for injectable regenerative therapies suggesting the translational significance in regenerative cardiology.</p>","PeriodicalId":72523,"journal":{"name":"Cardiology and cardiovascular medicine","volume":"6 5","pages":"466-472"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534332/pdf/nihms-1837495.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33492824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}