The kidney is important for regulating fluid and electrolyte balance, and it also secretes proteins that have important biological roles. In a study appearing online on April 7 in advance of the print publication of the May 1 issue of the Journal of Clinical Investigation, Jianchao Xu and colleagues from Yale University searched for novel proteins secreted by the kidney.
The researchers have identified a new protein, called renalase. Renalase is secreted by the kidney into the blood and regulates heart rate and blood pressure. Interestingly, renalase levels are markedly reduced in patients with end-stage kidney disease as compared to healthy subjects. Therefore, there may be a causal link between reduced renalase and the increased cardiovascular risk that is often seen in patients with renal disease
The identification of renalase not only provides a more complete understanding of renal and cardiovascular physiology, but could also lead to the development of novel therapies for patients with chronic kidney disease.
TITLE: Renalase: a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure
AUTHOR CONTACT:
Jianchao Xu
Yale University School of Medicine, New Haven, CT USA
Phone: (203) 932-5711, extension 2542; Fax: (203) 785-4904; E-mail: jianchao.xu@yale.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=24066
PHYSIOLOGY
With a WNK and a smile, blood pressure is under control
Familial hyperkalemic hypertension (FHHt) is a disease caused by mutations in 2 genes called WNK1 and WNK4. Patients have elevated blood pressure and high levels of potassium in their blood. In a study appearing online on April 7 in advance of the print publication of the May 1 issue of the Journal of Clinical Investigation, David Ellis and colleagues from Oregon Health and Science University provide an elegant dissection of the interactions of WNK1 and WNK4. The researchers show that the WNK proteins regulate human blood pressure by controlling salt excretion from the kidney. The findings provide insight into the relationship between WNK1 and WNK4 and also into FHHt.
TITLE: Mechanisms of WNK1 and WNK4 interaction to regulate thiazide-sensitive Na-Cl cotransport
AUTHOR CONTACT:
David H. Ellison
Oregon Health Sciences University, Portland, OR USA
Phone: (503) 494-8490; Fax: (503) 494-5330; E-mail: ellisond@ohsu.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=22452
PHYSIOLOGY
The A B Cs of Tangier Disease
High levels of HDL, the "good" cholesterol, are associated with low cardiovascular disease risk. Patients with Tangier disease have very low levels of HDL due to mutations in a protein called ABCA1. Exactly how ABCA1 controls HDL formation was not clear. In a study appearing online on April 7 in advance of the print publication of the May 1 issue of the Journal of Clinical Investigation, John Parks and colleagues from Wake Forest University describe a new mouse model that can be used to make liver-specific deletions of ABCA1. The mice have an 80% decrease in plasma HDL levels. This is the first proof that liver ABCA1 is critically important for normal HDL metabolism and may explain why normal HDL is broken down extensively in Tangier patients.
TITLE: Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I
AUTHOR CONTACT:
John S. Parks
Wake Forest University School of Medicine, Winston-Salem, NC USA
Phone: (336) 716-2145; Fax: (336) 716-6279; E-mail: jparks@wfubmc.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=23915
PHYSIOLOGY
CD36 greases up fat secretion and clearance
CD36 is a protein involved in many cellular processes but its role in regulating lipids derived from the intestine was unknown. CD36-deficient humans have abnormal blood lipid profiles. In a study appearing online on April 7 in advance of the print publication of the May 1 issue of the Journal of Clinical Investigation, Nada Abumrad and colleagues from Washington University show that CD36 deficiency in the mouse impairs lipid secretion by the small intestine. These findings raise the possibility that CD36 deficiency, by impairing clearance of fatty acids and triglycerides, may alter susceptibility to diabetes and atherosclerosis.
TITLE: CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood
AUTHOR CONTACT:
Nada A. Abumrad
Washington University, St. Louis, MO USA
Phone: (314) 747-0348; Fax: (314) 444-3432; E-mail: nabumrad@wustl.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=21514
IMMUNOLOGY
Vaccines get a boost from IL-7
Hope for controlling chronic diseases like cancer and HIV relies on development of useful vaccines that boost immune responses. In a study appearing online on April 7 in advance of the print publication of the May 1 issue of the Journal of Clinical Investigation, Crystal Mackall and colleagues from the NIH demonstrate that a limited exposure to either IL-7 or IL-15 protein at the time of immunization dramatically enhances immune cell responses. This work provides a compelling basis for use of IL-7 in vaccines to improve the immune response in situations where current vaccines are suboptimal such as for chronic infections or cancer,. As IL7 has just entered clinical trials, this work is timely and will be of great interest to the vaccine community at large.
TITLE: Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool
AUTHOR CONTACT:
Crystal L. Mackall
National Institutes of Health, Bethesda, MD USA
Phone: (301) 402-5940; Fax: (301) 402-0575; E-mail: cm35c@nih.gov
View the PDF of this article at: https://www.the-jci.org/article.php?id=23134
Journal
Journal of Clinical Investigation