RESUMEN
Mitochondrial dysfunction is a hallmark of heart failure. Mitochondrial transplantation has been demonstrated to be able to restore heart function, but its mechanism of action remains unresolved. Using an in-house optimized mitochondrial isolation method, we tested efficacy of mitochondria transplantation in two different heart failure models. First, using a doxorubicin-induced heart failure model, we demonstrate that mitochondrial transplantation before doxorubicin challenge protects cardiac function in vivo and prevents myocardial apoptosis, but contraction improvement relies on the metabolic compatibility between transplanted mitochondria and treated cardiomyocytes. Second, using a mutation-driven dilated cardiomyopathic human induced pluripotent stem cell-derived cardiomyocyte model, we demonstrate that mitochondrial transplantation preferentially boosts contraction in the ventricular myocytes. Last, using single-cell RNA-seq, we show that mitochondria transplantation boosts contractility in dystrophic cardiomyocytes with few transcriptomic alterations. Together, we provide evidence that mitochondria transplantation confers myocardial protection and may serve as a potential therapeutic option for heart failure.
Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Células Madre Pluripotentes Inducidas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Cardiomiopatías/metabolismo , Mitocondrias/metabolismo , Doxorrubicina/efectos adversos , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
Male-factor infertility is a common but stigmatised issue, and men often do not receive the emotional support and the information they need. This study sought to understand awareness of male fertility issues compared to female fertility among the UK general male public, and also what were perceived as being the optimum methods for providing support for affected men, emotionally and through information. Men feel that male infertility is not discussed by the public as much as female infertility. Lifestyle issues that affect male fertility are not well understood, and men affected by infertility desire more support, including online, from health professionals and through peer support. Health professionals, including those in public health, could offer evidence-based programmes to reduce stigma and increase public knowledge about infertility, as well as offer emotional support to men with infertility problems.