Neuregulin-1 improves right ventricular function and attenuates experimental pulmonary arterial hypertension.

AIMS: Pulmonary arterial hypertension (PAH) is a serious disease that affects both the pulmonary vasculature and the right ventricle (RV). Current treatment options are insufficient. The cardiac neuregulin (NRG)-1/ErbB system is deregulated during heart failure, and treatment with recombinant human NRG-1 (rhNRG-1) has been shown to be beneficial in animal models and in patients with left ventricular (LV) dysfunction. This study aimed to evaluate the effects of rhNRG-1 in RV function and pulmonary vasculature in monocrotaline (MCT)-induced PAH and RV hypertrophy (RVH). METHODS AND RESULTS: Male wistar rats (7- to 8-weeks old, n = 78) were injected with MCT (60 mg/kg, s.c.) or saline and treated with rhNRG-1 (40 µg/kg/day) or vehicle for 1 week, starting 2 weeks after MCT administration. Another set of animals was submitted to pulmonary artery banding (PAB) or sham surgery, and followed the same protocol. MCT administration resulted in the development of PAH, pulmonary arterial and RV remodelling, and dysfunction, and increased RV markers of cardiac damage. Treatment with rhNRG-1 attenuated RVH, improved RV function, and decreased RV expression of disease markers. Moreover, rhNRG-1 decreased pulmonary vascular remodelling and attenuated MCT-induced endothelial dysfunction. The anti-remodelling effects of rhNRG-1 were confirmed in the PAB model, where rhNRG-1 treatment was able to attenuate PAB-induced RVH. CONCLUSION: rhNRG-1 treatment attenuates pulmonary arterial and RV remodelling, and dysfunction in a rat model of MCT-induced PAH and has direct anti-remodelling effects on the pressure-overloaded RV.

Adipokines and their receptors: potential new targets in cardiovascular diseases.

Adipose tissue is an 'endocrine organ' that influences diverse physiological and pathological processes via adipokines secretion. Strong evidences suggest that epicardial and perivascular adipose tissue can directly regulate heart and vessels' structure and function. Indeed, in obesity there is a shift toward the secretion of adipokines that promote a pro-inflammatory status and contribute to obesity cardiomyopathy. The prospect of modulating adipokines and/or their receptors represents an attractive perspective to the treatment of cardiovascular diseases. In this paper, we described the most important actions of certain adipokines and their receptors that are capable of influencing cardiovascular physiology as well as their possible use as therapeutic targets.

Systematic Review of the Relation Between Intestinal Microbiota and Toll-Like Receptors in the Metabolic Syndrome: What Do We Know So Far?

INTRODUCTION: Metabolic syndrome is an emerging problem in developed countries and presents itself as a potential threat worldwide. The role of diabetes, dyslipidaemia and hepatic steatosis as pivotal components of the metabolic syndrome is well known. However, their common persistent chronic inflammation and its potential cause still elude. This systematic review aims to present evidence of the mechanisms that link the intestinal microbioma, innate immunity and metabolic syndrome. METHODS: A comprehensive research was made using PubMed database and 35 articles were selected. RESULTS: We found that metabolic syndrome is associated to increased levels of innate immunity receptors, namely, Toll-like receptors, both in intestine and systemically and its polymorphisms may change the risk of metabolic syndrome development. Microbioma dysbiosis is also present in metabolic syndrome, with lower prevalence of Bacteroidetes and increased prevalence of Firmicutes populations. The data suggest that the link between intestinal microbiota and Toll-like receptors can negatively endanger the metabolic homeostasis. CONCLUSION: Current evidence suggests that innate immunity and intestinal microbiota may be the hidden link in the metabolic syndrome development mechanisms. In the near future, this can be the key in the development of new prophylactic and therapeutic strategies to treat metabolic syndrome patients.

INTRODUÇÃO: A síndrome metabólica é, hoje, um problema emergente nos países desenvolvidos e apresenta-se como uma das principais ameaças médicas à escala global. O papel desempenhado pela diabetes, dislipidemia e a esteatose hepática, como componentes principais desta Síndrome é prontamente reconhecido. No entanto, a inflamação crónica persistente comum e as suas potenciais causas ainda não estão claramente definidas. OBJECTIVOS: Esta revisão sistemática pretende apresentar evidências dos mecanismos que interligam o microbioma intestinal, a imunidade inata e a síndrome metabólica. MÉTODOS: Uma pesquisa sistemática foi realizada, utilizando a base de dados PubMed, tendo selecionado 35 artigos para a elaboração desta revisão. RESULTADOS: A síndrome metabólica está claramente associada a níveis aumentados de expressão dos receptores da imunidade inata, nomeadamente, os receptores da família Toll-like receptors, quer no tecido intestinal, quer sistemicamente, e diferentes polimorfismos parecem ser responsáveis por diferentes riscos de desenvolver esta doença. Por outro lado, a disbiose do microbioma intestinal está também presente na síndrome metabólica, com a presença de Bacteriodetes em menor prevalência e com aumento das populações de Firmicutes. Os resultados sugerem ainda que a ligação entre a microbiota intestinal e os receptores da imunidade inata possa negativamente comprometer a homeostasia metabólica, de forma semelhante à evidenciada nesta síndrome. CONCLUSÕES: Evidência actual sugere e suporta que a imunidade inata e a microbiota intestinal possam ser a ligação pivô nos mecanismos de desenvolvimento da síndrome metabólica. Num futuro próximo, esta pode ser a chave para o desenvolvimento de novas estratégias profiláticas e terapêuticas para a síndrome metabólica.