scholarly journals Benchmarking evolutionary tinkering underlying human–viral molecular mimicry shows multiple host pulmonary–arterial peptides mimicked by SARS-CoV-2

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
A. J. Venkatakrishnan ◽  
Nikhil Kayal ◽  
Praveen Anand ◽  
Andrew D. Badley ◽  
George M. Church ◽  
...  
Keyword(s):  
Molecular Mimicry ◽  
Herd Immunity ◽  
Computational Framework ◽  
Human Lungs ◽  
Human Proteins ◽  
Peptide Mimicry ◽  
Pulmonary Arterial ◽  
Binding Peptides ◽  
Human Viruses

Abstract The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. Here, we report 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and the human reference proteome. We benchmark this observation against other viral–human 8-mer/9-mer peptide identity, which suggests generally similar extents of molecular mimicry for SARS-CoV-2 and many other human viruses. Interestingly, 20 novel human peptides mimicked by SARS-CoV-2 have not been observed in any previous coronavirus strains (HCoV, SARS-CoV, and MERS). Furthermore, four of the human 8-mer/9-mer peptides mimicked by SARS-CoV-2 map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by single-cell RNA-seq (scRNA-seq) analysis that shows the targeted genes significantly expressed in human lungs and arteries; tissues implicated in COVID-19 pathogenesis. Finally, HLA-A*03 restricted 8-mer peptides are found to be shared broadly by human and coronaviridae helicases in functional hotspots, with potential implications for nucleic acid unwinding upon initial infection. This study presents the first scan of human peptide mimicry by SARS-CoV-2, and via its benchmarking against human–viral mimicry more broadly, presents a computational framework for follow-up studies to assay how evolutionary tinkering may relate to zoonosis and herd immunity.

scholarly journals Multi-pronged human protein mimicry by SARS-CoV-2 reveals bifurcating potential for MHC detection and immune evasion

2020 ◽  
Author(s):  
AJ Venkatakrishnan ◽  
Nikhil Kayal ◽  
Praveen Anand ◽  
Andrew D. Badley ◽  
George M. Church ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Immune Cells ◽  
Molecular Mimicry ◽  
Human Proteome ◽  
Human Coronavirus ◽  
Human Proteins ◽  
Peptide Mimicry ◽  
Binding Peptides ◽  
Viral Mimicry

The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. We identify 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and human proteomes, along similar extents of viral mimicry observed in other viruses. Interestingly, 20 novel peptides have not been observed in any previous human coronavirus (HCoV) strains. Four of the total mimicked 8-mers/9-mers map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This mimicry of multiple human proteins by SARS-CoV-2 is made salient by the targeted genes being focally expressed in arteries, lungs, esophagus, pancreas, and macrophages. Further, HLA-A*03 restricted 8-mer peptides are shared broadly by human and coronaviridae helicases with primary expression of the mimicked human proteins in the neurons and immune cells. This study presents the first comprehensive scan of peptide mimicry by SARS-CoV-2 of the human proteome and motivates follow-up research into its immunological consequences.

Surgical Strategy in Patients with Atrial Septal Defect and Severe Pulmonary Hypertension

2012 ◽  
Vol 15 (2) ◽  
pp. 111 ◽  
Author(s):  
Yang Hyun Cho ◽  
Tae-Gook Jun ◽  
Ji-Hyuk Yang ◽  
Pyo Won Park ◽  
June Huh ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Atrial Septal Defect ◽  
Tricuspid Regurgitation ◽  
Septal Defect ◽  
Maze Procedure ◽  
Severe Pulmonary Hypertension ◽  
Tricuspid Annuloplasty ◽  
Pulmonary Arterial ◽  
Asd Closure

The aim of the study was to review our experience with atrial septal defect (ASD) closure with a fenestrated patch in patients with severe pulmonary hypertension. Between July 2004 and February 2009, 16 patients with isolated ASD underwent closure with a fenestrated patch. All patients had a secundum type ASD and severe pulmonary hypertension. Patients ranged in age from 6 to 57 years (mean � SD, 34.9 � 13.5 years). The follow-up period was 9 to 59 months (mean, 34.5 � 13.1 months). The ranges of preoperative systolic and pulmonary arterial pressures were 63 to 119 mm Hg (mean, 83.8 � 13.9 mm Hg) and 37 to 77 mm Hg (mean, 51.1 � 10.1 mm Hg). The ranges of preoperative values for the ratio of the pulmonary flow to the systemic flow and for pulmonary arterial resistance were 1.1 to 2.7 (mean, 1.95 � 0.5) and 3.9 to 16.7 Wood units (mean, 9.8 � 2.9 Wood units), respectively. There was no early or late mortality. Tricuspid annuloplasty was performed in 14 patients (87.5%). The peak tricuspid regurgitation gradient and the ratio of the systolic pulmonary artery pressure to the systemic arterial pressure were decreased in all patients. The New York Heart Association class and the grade of tricuspid regurgitation were improved in 13 patients (81.2%) and 15 patients (93.7%), respectively. ASD closure in patients with severe pulmonary hypertension can be performed safely if we create fenestration. Tricuspid annuloplasty and a Cox maze procedure may improve the clinical result. Close observation and follow-up will be needed to validate the long-term benefits.

scholarly journals Plasma exosomal miR-596: a novel biomarker predicts survival in patients with idiopathic pulmonary artery hypertension

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052110023
Author(s):  
Yang Huang ◽  
Zuo-Gang Wang ◽  
Liang Tang ◽  
Su-Gang Gong ◽  
Yuan-Yuan Sun ◽  
...  
Keyword(s):  
Right Heart Catheterization ◽  
Pulmonary Artery Hypertension ◽  
Right Atrial ◽  
Heart Catheterization ◽  
Distribution Analysis ◽  
Poor Overall Survival ◽  
Transmission Electron ◽  
Exosomal Mirnas ◽  
Pulmonary Arterial

Objective To determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods The study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction. Results This study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival. Conclusions High levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.

Change of myocardial fluorodeoxyglucose uptake distribution after specific therapy of pulmonary arterial hypertension patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Kazimierczyk ◽  
P Szumowski ◽  
L.M Malek ◽  
P Blaszczak ◽  
D Jurgilewicz ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Glucose Uptake ◽  
Funding Source ◽  
Hemodynamic Parameters ◽  
Fdg Uptake ◽  
Baseline Visit ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Background Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). In our previous study, we confirmed that increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) (presented as higher ratio of FDG uptake of RV to LV) was associated with progressive RV dysfunction and preceded hemodynamic and clinical deterioration in PAH patients. Now, we obtained second PET/MRI assessments of the study group after 2-years of PAH-targeted treatment. Aim The aim of the study was to obtain change of cardiac FDG uptake in PAH patients after follow-up period and to indicate factors mainly affecting this change. Methods Twenty-eight PAH patients (51.32±15.91 years) had simultaneous PET/MRI scans performed during baseline visit. FDG was used and its uptake was quantified as mean standardized uptake value (SUV) for both left (LV) and RV. Second PET/MRI assessments were done after 2 years in the group of twenty patients (four deaths, four patients did not agree to perform additional scans). Results After follow-up period, we observed significant change of MRI-derived RV ejection fraction (45±10% to 51.2±12.7%, p=0.03), and improvement in hemodynamic parameters obtained from right heart catheterization (RHC) e.g. mean pulmonary artery pressure, mPAP (48.5±17.2 to 41.8±17.1 mmHg, p=0.01) and pulmonary vascular resistance, PVR (8.7±5.3 to 7.0±4.2 WU, p=0.04). Follow-up SUVRV/SUVLV ratio significantly correlated with follow-up RV hemodynamic parameters confirming relationship between RV function and cardiac metabolic alterations (Table 1). Interestingly, patients who had improvement in SUVRV/SUVLV (lower follow-up value than baseline, n=11) had significantly higher mPAP at baseline visit (58.9±18.7 vs 40.3±11.8 mmHg, p=0.02), suggesting that RV FDG accumulation in advanced PAH may decrease after the PAH-specific treatment in accordance with the degree of reduction in the pulmonary vascular resistance. Conclusion Impaired RV function is associated with increased glucose uptake of RV myocytes estimated by FDG PET in PAH patients. Targeted treatment may improve RV function and thus affect previously altered cardiac glucose uptake. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Polish National Science Centre

Scimittar Syndrome; Right time to operate? and mid-term results.

2021 ◽  
Author(s):  
Kenan Abdurrahman Kara ◽  
Ergi̇n Arslanoğlu ◽  
Fatih Tomrukçu ◽  
Abdullah Arif Yılmaz ◽  
Fatih Yiğit ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Artery Hypertension ◽  
Scimitar Syndrome ◽  
Pulmonary Arterial ◽  
The Right ◽  
Vein Stenosis ◽  
Mid Term Results

Objectives: Scimitar syndrome is a combination of rare congenital cardiopulmonary anomalies that can occur in 3% to 6% of patients with a partial abnormal venous connection. The presence of accompanying cardiac anomalies in these patients and in cases such as severe hypoplasia of the right lung or accompanying pulmonary artery hypertension necessitate early surgery in early infancy. Patients and Methods: 9 patients with scimitar syndrome operated on in our pediatric cardiac surgery clinic from 2012 to 2020 were retrospectively examined in our study. The ages of the patients ranged from 1 to 47 years, with a mean of 18.11±14.44. 1 patient died and mortality was 11.11%. Of the patients, 4 were male (44.44%) and 5 were female (55.56%). Patients' pulmonary arterial pressure ranged from 0.15 to 94 mmHg, with a mean of 39.22 ±22.49. Results: Close to 25% scimitar vein stenosis or scimitar vein drainage occlusion has been reported in the postoperative period, mostly in the newborn group in the literature. 2 patients had non-critical stenosis during the 3rd year follow-up despite the absence of stenosis orocclusion during the first 2 years of follow-up of 9 patients we followed. Their surgical follow-up is still ongoing since they are asymptomatic. Conclusion: As a result, the course of the disease depends on the follow-up of the patient, the timing of the surgery, and the quality of the anastomosis. The follow-up and treatment of these patients will be more accurate in advanced centers experienced in scimitar surgery.

Characterization and treatment of systemic venous to pulmonary venous collaterals seen after the Fontan operation

2003 ◽  
Vol 13 (5) ◽  
pp. 424-430 ◽  
Author(s):  
Hisashi Sugiyama ◽  
Shi-Joon Yoo ◽  
William Williams ◽  
Lee N. Benson
Keyword(s):  
Fontan Operation ◽  
Fontan Circulation ◽  
Brachiocephalic Vein ◽  
Interventional Treatment ◽  
Mean Pulmonary Arterial Pressure ◽  
Venous Collaterals ◽  
Pulmonary Arterial ◽  
Transcatheter Interventions ◽  
Cardiac Catherization

Objectives: To determine the anatomical characteristics of systemic venous collaterals formed after the Fontan operation, and the efficacy of a transcatheter strategy for management. Methods: We reviewed retrospectively the data from cardiac catherization of 50 persistently cyanotic patients after the Fontan operation. Results: A total of 54 transcatheter interventions were performed, at a mean age of 6.3 ± 3.5 years, a mean interval of 2.7 ± 2.9 years from completion of the Fontan circulation. Of 38 patients who had fenestration of the baffle at the time of surgery, 25 had patency of the fenestration, and 24 had the fenestration occluded with a device at the time of interventional treatment for associated venous collaterals. We identified a total of 68 systemic venous collateral channels, of which 36 (53%) were supracardiac, 12 (18%) cardiac, and 20 (29%) infracardiac in origin. The most common site of origin was the brachiocephalic vein (44%), followed by the left phrenic vein (25%). A longer time from surgery, at 3.3 ± 3.4 years, was associated with the identification of collaterals having a diameter larger than 4 mm (p < 0.01). The mean pulmonary arterial pressure was higher in those with larger compared to those with smaller collaterals (13.3 ± 2.8 versus 11.1 ± 2.0 mmHg, p < 0.01). Coils were used for occlusion of 61 vessels, and a Rashkind™ occluder for the remaining 7. After exclusion of the patients undergoing simultaneous closure of their fenestration, systemic saturation of oxygen increased from 89 ± 6% to 95 ± 3% (p < 0.01). Conclusion: Venous collateral channels are common in patients suffering progressive cyanosis in the setting of the Fontan circulation. The collaterals increase in size with time, and are associated with higher pulmonary arterial pressures. Transcatheter treatment is feasible, and results in resolution of cyanosis. Only continuing follow-up will show whether further collateralization occurs in time.

Sign in / Sign up

Export Citation Format

Share Document