The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.

AimStroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%–80% of all strokes. It is of considerable significance to carry out multidimensional management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases.MethodsWe had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years.ResultsThis evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management.ConclusionsThis updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.

Adipokines play important roles in metabolic homeostasis and disease. We have recently identified a novel adipokine Metrnl, also known as Subfatin, for its high expression in subcutaneous fat. Here, we demonstrate a prodifferentiation action of Metrnl in white adipocytes. Adipocyte-specific knockout of Metrnl exacerbates insulin resistance induced by high-fat diet (HFD), whereas adipocyte-specific transgenic overexpression of Metrnl prevents insulin resistance induced by HFD or leptin deletion. Body weight and adipose content are not changed by adipocyte Metrnl. Consistently, no correlation is found between serum Metrnl level and BMI in humans. Metrnl promotes white adipocyte differentiation, expandability, and lipid metabolism and inhibits adipose inflammation to form functional fat, which contributes to its activity against insulin resistance. The insulin sensitization of Metrnl is blocked by PPARγ inhibitors or knockdown. However, Metrnl does not drive white adipose browning. Acute intravenous injection of recombinant Metrnl has no hypoglycemic effect, and 1-week intravenous administration of Metrnl is unable to rescue insulin resistance exacerbated by adipocyte Metrnl deficiency. Our results suggest adipocyte Metrnl controls insulin sensitivity at least via its local autocrine/paracrine action through the PPARγ pathway. Adipocyte Metrnl is an inherent insulin sensitizer and may become a therapeutic target for insulin resistance.