Medical Reading

News From The Journal Of Clinical Investigation: Oct. 1, 2010

May 11, 2017

CARDIOVASCULAR DISEASE: How the drugs work to reduce mortality in blood vessel disease

Drugs that antagonize the hormone aldosterone have been shown in clinical trails to reduce mortality in individuals with atherosclerosis - a disease sometimes known as hardening of the arteries that is a major cause of heart attack and stroke. Aldosterone increases blood pressure via effects on the protein MR, but the beneficial effects of aldosterone antagonists in individuals with atherosclerosis far outweighed their modest effect on blood pressure. It has therefore been suggested that aldosterone has more direct atherosclerosis-promoting effects. One such effect has now been uncovered by a team of researchers led by Iris Jaffe, at Tufts Medical Center, Boston. Specifically, the team found that aldosterone, via effects on MR, induces expression of the protein PGF in mouse and human blood vessel walls and that PGF augments blood vessel injury. The team therefore suggest that targeting the blood vessel aldosterone/MR/PGF pathway might provide a new approach to reducing mortality in individuals with atherosclerosis.

TITLE: Placental growth factor mediates aldosterone-dependent vascular injury in mice

NEPHROLOGY: Promoting progression to kidney failure

Chronic kidney disease (the slow loss of kidney function over time) is a major healthcare burden. In the United States, it is estimated that more than 20 million adults have significantly reduced kidney function. New research, in mice and humans, led by Fabiola Terzi, at INSERM U845, Hôpital Necker Enfants Malades, France, has now identified the protein lipocalin 2 as a player in progression of chronic kidney disease to end-stage kidney failure, a condition requiring dialysis or transplantation. As lipocalin 2 levels were found to be increased particularly in patients who rapidly progressed to end-stage kidney failure, the authors suggest that it is worth studying in large patient cohorts whether lipocalin 2 is a good biomarker of progression of chronic kidney disease to end-stage kidney failure. Identifying such individuals might allow clinicians to intervene more aggressively and postpone kidney failure.

TITLE: Lipocalin 2 is essential for chronic kidney disease progression in mice and humans

HEMATOLOGY: Fanconi anemia cells can't divide

The main cause of death for individuals with the rare genetic disorder Fanconi anemia is depletion of bone marrow cells, which leads to bone marrow failure. Fanconi anemia is caused by mutations in any one of several genes that generate proteins that cooperate in a DNA repair pathway known as the Fanconi anemia pathway. New data, generated by Alan D'Andrea and colleagues, at the Dana-Farber Cancer Institute, Boston, now indicates that the Fanconi anemia pathway is involved in mouse and human bone marrow cell division. They therefore propose that the depletion of bone marrow cells in individuals with Fanconi anemia could be due, at least in part, to a failure of bone marrow cells to divide, a cellular defect associated with apoptotic cell death.

TITLE: Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cells

METABOLIC DISEASE: The protein MKP-3: a new drug target for diabetes?

Type 2 diabetes is usually preceded by resistance to the hormone insulin, which regulates levels of glucose in the blood. Excessive production of glucose by the liver is a key factor in progression to type 2 diabetes in individuals who are resistant to the effects of insulin. Recent in vitro data indicate that the protein MKP-3 can promote the expression of genes involved in the generation of glucose by the liver, but whether this is true in vivo was not assessed. Now, a team of researchers, led by Zhidan Wu, at Novartis Institutes for BioMedical Research, Cambridge, and Haiyan Xu, at Brown Medical School, Providence, has shown in mice that MKP-3 promotes the production of glucose by the liver in vivo. The team therefore suggests that MKP-3 might provide a new therapeutic target for the treatment of obesity-related type 2 diabetes.

TITLE: MAPK phosphatase promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice

VIROLOGY: Profiling key antiviral responders

CD8+ T cells are key mediators of the immune response against viruses that invade our body. The fate of these cells after the initial antiviral response varies depending on the identity of the virus and on whether the virus is cleared from the body or persists. In the case of persistent human cytomegalovirus (HCMV) infection, a large number of virus-specific, quiescent, effector-type CD8+ T cells with constitutive killing activity remain after the initial immune response. New research, using HCMV-specific CD8+ T cells collected from patients infected with HCMV, led by René van Lier, at the Academic Medical Center, Amsterdam, the Netherlands, now suggests that the enduring effector cell properties of these cells are important in preventing reactivation of persistent HCMV.

TITLE: Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation

Karen Honey
Journal of Clinical Investigation