ABSTRACT
Pulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues.
Subject(s)
Cardiomegaly/physiopathology , Pulmonary Arterial Hypertension/diet therapy , Animals , Cardiomegaly/diet therapy , Disease Models, Animal , Female , Fibrosis/metabolism , Heart/physiopathology , Heart Ventricles/physiopathology , Hypertension, Pulmonary/physiopathology , Hypertrophy, Right Ventricular/diet therapy , Mice , Mice, Inbred C57BL , Monocrotaline/pharmacology , Muscle, Skeletal/metabolism , Pulmonary Arterial Hypertension/metabolism , Pulmonary Artery/pathology , Vascular Remodeling/drug effects , Ventricular Function, RightABSTRACT
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the pulmonary vasculature. Recent advances in pharmacotherapy improved life expectancy of PAH patients and, thus, signified the role of general measures, including diet, in the management of the disease. METHODS: In the present narrative review we will briefly summarize information about current and novel PAH therapies and analyze preclinical evidence on the influence of certain nutrients on the pathogenesis of PAH. RESULTS: Although the evidence on the role of dietary deficiencies in the development and progression of PAH in humans is limited, preclinical studies demonstrate that dietary components such as quercetin, genistein, n-3 PUFAs, vitamin D, coenzyme Q10 and resveratrol may influence various aspects of PAH pathobiology. CONCLUSIONS: Further research on the role of diet in PAH is needed. Taking into account pleiotropic and subtle effects of dietary constituents as well as the rare and severe nature of PAH, clinical studies on the disease-specific nutritional patterns rather than on single dietary components may help to reveal if diet can be an important tool to improve the efficacy of pharmacotherapy in PAH.