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1.
JCI Insight ; 6(16)2021 08 23.
Article in English | MEDLINE | ID: mdl-34283808

ABSTRACT

BACKGROUNDEpicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT's immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients.METHODSWe recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients' clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups.RESULTSFlow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls.CONCLUSIONAdaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile.FUNDINGBarts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.


Subject(s)
Adipose Tissue/immunology , Diabetes Mellitus/epidemiology , Obesity/epidemiology , Pericarditis/epidemiology , Pericardium/pathology , Adaptive Immunity , Adipose Tissue/cytology , Adipose Tissue/pathology , Aged , Cardiometabolic Risk Factors , Comorbidity , Coronary Artery Bypass , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Coronary Artery Disease/metabolism , Coronary Artery Disease/surgery , Diabetes Mellitus/blood , Diabetes Mellitus/immunology , Diabetes Mellitus/metabolism , Female , Humans , Immunophenotyping , Male , Middle Aged , Obesity/blood , Obesity/immunology , Obesity/metabolism , Pericarditis/immunology , Pericarditis/pathology , Pericardium/surgery , RNA-Seq
2.
BMJ Case Rep ; 13(2)2020 Feb 28.
Article in English | MEDLINE | ID: mdl-32114496

ABSTRACT

A 43-year-old man with Austrian syndrome, the triad of infective endocarditis (IE), pneumonia and meningitis caused by Streptococcus pneumoniae, underwent emergency aortic and mitral valve replacement and closure of an aortic root abscess. Postoperatively, he required mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation and an intra-aortic balloon pump. Several days after surgery, new mitral and aortic paraprosthetic leaks (PPLs) developed. These were managed conservatively, initially, but eventually required percutaneous closure 6 weeks after the initial operation. This has enabled the patient to recover to independent mobility, 20 weeks after the operation. This case illustrates a rare clinical syndrome and the devastating impact of IE. Moreover, it illustrates the successful application of extracorporeal membrane oxygenation in postcardiotomy cardiac failure and the successful treatment of PPL in a patient unfit for redo surgery.


Subject(s)
Endocarditis/microbiology , Endocarditis/therapy , Extracorporeal Membrane Oxygenation , Meningitis/microbiology , Meningitis/therapy , Pneumonia, Bacterial/therapy , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotics, Antitubercular/therapeutic use , Heart Valve Prosthesis , Humans , Intra-Aortic Balloon Pumping , Male , Streptococcus pneumoniae , Syndrome
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