ABSTRACT
BACKGROUND: Visceral obesity is directly linked to increased cardiovascular risk, including heart failure. OBJECTIVES: This study explored the ability of human epicardial adipose tissue (EAT)-derived microRNAs (miRNAs) to regulate the myocardial redox state and clinical outcomes. METHODS: This study screened for miRNAs expressed and released from human EAT and tested for correlations with the redox state in the adjacent myocardium in paired EAT/atrial biopsy specimens from patients undergoing cardiac surgery. Three miRNAs were then tested for causality in an in vitro model of cardiomyocytes. At a clinical level, causality/directionality were tested using genome-wide association screening, and the underlying mechanisms were explored using human biopsy specimens, as well as overexpression of the candidate miRNAs and their targets in vitro and in vivo using a transgenic mouse model. The final prognostic value of the discovered targets was tested in patients undergoing cardiac surgery, followed up for a median of 8 years. RESULTS: EAT miR-92a-3p was related to lower oxidative stress in human myocardium, a finding confirmed by using genetic regulators of miR-92a-3p in the human heart and EAT. miR-92a-3p reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase-derived superoxide (O2.-) by targeting myocardial expression of WNT5A, which regulated Rac1-dependent activation of NADPH oxidases. Finally, high miR-92a-3p levels in EAT were independently related with lower risk of adverse cardiovascular events. CONCLUSIONS: EAT-derived miRNAs exert paracrine effects on the human heart. Indeed miR-92a-3p suppresses the wingless-type MMTV integration site family, member 5a/Rac1/NADPH oxidase axis and improves the myocardial redox state. EAT-derived miR-92a-3p is related to improved clinical outcomes and is a rational therapeutic target for the prevention and treatment of obesity-related heart disease.
Subject(s)
Genome-Wide Association Study , MicroRNAs , Humans , Mice , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Myocardium/metabolism , Oxidation-Reduction , Mice, Transgenic , Adipose Tissue/metabolismABSTRACT
Minimally invasive mitral surgery is increasingly recognized as routine. We describe here the financially economical set-up for totally endoscopic surgery, which also represents currently the smallest surgical access, limited only by prosthesis and retractor size. This allows the full range of repairs to be performed. Cannulation for cardiopulmonary bypass is performed via the groin. A cosmetic, periareolar (in males) or inframammary fold (in females) incision is made and the chest entered on bypass. An aortic cross-clamp and crystalloid cardioplegia are used via the aortic root prior to atriotomy and surgical repair. This method gives the highest level of cosmesis available and minimal discomfort, without compromising on the extremely good published results.
Subject(s)
Endoscopy/methods , Heart Valve Prosthesis Implantation/methods , Mitral Valve Insufficiency/surgery , Adult , Aged , Endoscopy/instrumentation , Female , Heart Valve Prosthesis Implantation/instrumentation , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
We present the surgical resection and repair, using port-access, in a case of extensive lipomatous hypertrophy of the interatrial septum (IAS). There was tumourous lipomatous hypertrophy on the superior vena cava (SVC) - atrial junction close to the aortic root beside massive IAS hypertrophy. Resection of involved IAS and SVC was performed using bovine pericardium for the repair.
