JCI table of contents: Nov. 1, 2007

TITLE: OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice

AUTHOR CONTACT:
Toshiaki Kikuchi
Tohoku University, Sendai, Japan.
Phone: 81-22-717-8539; Fax: 81-22-717-8549; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=32693

ACCOMPANYING COMMENTARY

TITLE: OX40 signaling directly triggers the antitumor effects of NKT cells

AUTHOR CONTACT:
Dapeng Zhou
University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Phone: (713) 792-3134; Fax: (713) 563-3424; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33976

CARDIOLOGY: New insight into heart diseases: coupling blood vessel growth and increased heart size

The heart is able to respond to its surroundings; so, if more power is needed to pump the blood around the body it can increase the size of the muscle cells of the heart (a process known as cardiac hypertrophy). Cardiac hypertrophy can be pathological (i.e. associated with increased morbidity and mortality), such as in individuals with high blood pressure, or physiological (i.e. not associated with impaired heart function), such as in trained athletes. In the November issue of the Journal of Clinical Investigation, two studies in mice provide new insight into the link between cardiac hypertrophy and the growth of new blood vessels (a process known as angiogenesis). As discussed in the accompanying commentary by Kenneth Walsh and Ichiro Shiojima, these reports suggest that cardiac hypertrophy is driven by interactions between heart muscle cells (myocytes) and blood vessel cells (endothelial cells). This challenges the idea that cardiac hypertrophy is myocyte driven and might lead to the development of new therapeutics for the treatment of heat diseases.

In the first study, Jeffery Molkentin and colleagues from Cincinnati Children's Hospital Medical Center, showed that expression of the protein GATA4 in mouse myocytes promotes angiogenesis in the heart under pathological and physiological conditions. The induction of angiogenesis was mediated by upregulation of myocyte expression of VEGF-A, which acted on endothelial cells to promote angiogenesis. As previous studies have indicated that GATA4 activity in the heart is increased by factors that induce hypertrophy, these data show that GATA4 has a central role in inducing the angiogenesis in the heart that is associated with cardiac hypertrophy.

Michael Simons and colleagues from Dartmouth Medical School, Hanover, provided a more direct link between cardiac hypertrophy and angiogenesis in the mouse heart. Expression for 3 weeks in myocytes of the secreted angiogenic growth factor PR39 induced an increase in the mass of blood vessels in the heart. However, if expression was maintained for 6 weeks, the increased angiogenesis was accompanied by cardiac hypertrophy in the absence of pathological stimuli of cardiac hypertrophy. These data indicate that angiogenesis in the normal mouse heart can drive cardiac hypertrophy and further analysis indicated that this process is driven by nitric oxide.