RESUMEN
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.
Asunto(s)
Tejido Adiposo/inmunología , Diabetes Mellitus/epidemiología , Obesidad/epidemiología , Pericarditis/epidemiología , Pericardio/patología , Inmunidad Adaptativa , Tejido Adiposo/citología , Tejido Adiposo/patología , Anciano , Factores de Riesgo Cardiometabólico , Comorbilidad , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/cirugía , Diabetes Mellitus/sangre , Diabetes Mellitus/inmunología , Diabetes Mellitus/metabolismo , Femenino , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/inmunología , Obesidad/metabolismo , Pericarditis/inmunología , Pericarditis/patología , Pericardio/cirugía , RNA-SeqRESUMEN
The aim of the study was to assess the effect of transmyocardial laser revascularization (TMLR) alone and in combination with coronary artery bypass grafting (CABG) on the angina score (CCS--Canadian Cardiovascular Society class), exercise tolerance and left ventricular function 6 months after the procedures. Sixty two patients were subjected to revascularization, 38 to sole TMLR procedure and 24 to combination CABG and TMLR (CABG/TMLR group). The angina score and exercise stress test together with radionuclide ventriculography were performed before and 6 months after the operation. The angina class and exercise tolerance were similar in both groups preoperatively. After the operation the improvement was seen in both groups with no statistical difference. The left ventricular ejection fraction were 61 +/- 8% and 54 +/- 8% (p < 0.05) before operation and after 6 months respectively. Transmyocardial laser revascularisation alone and in combination with coronary artery bypass grafting may relieve the angina and improve the exercise tolerance. However the left ventricular ejection fraction may drop significantly.
Asunto(s)
Puente de Arteria Coronaria/métodos , Terapia por Láser/métodos , Infarto del Miocardio/cirugía , Revascularización Miocárdica/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Encuestas y CuestionariosRESUMEN
AIM: To analyse the clinical outcome and myocardial perfusion and function after transmyocardial revascularisation (TMR) in patients with normal left ventricular function and multivessel coronary artery disease non-amenable for standard revascularisation. METHOD AND RESULTS: Twenty three severely symptomatic patients (CCS score median 4) with normal left ventricular systolic function but coronaries non-amenable for either PTCA or CABG were subjected to TMR. The angina score, left ventricular systolic and diastolic function in radionuclide ventriculography at rest, exercise tolerance and myocardial perfusion--Thallium-201 SPECT (adenosine stress 74 and 37 MBq under nitrate cover) were evaluated before and 3, 6, 12 months post-operatively. After an average of 40 +/- 12 (range 14-56) TMR channels angina score decreased significantly (p< 0.0001) and the exercise tolerance increased (from 6.0 +/- 4.5 to 9.1 +/- 4.6 after 6 months, p< 0.05) in 21 patients. During the follow up period two patients had a myocardial infarction and one committed suicide after 6 months. Ejection fraction dropped significantly only after 1 year post-TMR from 70 +/- 13 to 63 +/- 0.13%, p < 0.05. The overall perfusion improved initially in 14 patients with subsequent deterioration in time. The changes in segmental perfusion were not associated with the symptomatic improvement. CONCLUSION: Transmyocardial revascularisation in patients with normal ejection fraction may improve the angina class, exercise tolerance and overall but not segmental perfusion and does not show any immediate effect on left ventricular function.