Akt is a molecule involved in many cellular functions, including growth, survival, and metabolism. Akt exists in three isoforms – Akt1, Akt2, and Akt3, which have a substantial degree of functional overlap. In the heart and vasculature, Akt may be protective against ischemia and it may enhance cardiac function after heart failure. But Akt may also have detrimental effects.
In our August 1 issue, the Journal of Clinical Investigation presents three research papers that explore Akt1 in the heart, plus an accompanying commentary. The first paper, by Anthony Rosenzweig and colleagues at Harvard, and the second paper by Kenneth Walsh and colleagues at Boston University, both provide new insights into how Akt1 can be maladaptive in the heart. Both studies use transgenic mice that overexpress active Akt1 to show that this causes cardiac dysfunction, including hypertrophy and fibrosis.
The third paper in this issue, by William Sessa and colleagues at Yale University, explores which Akt isoform is responsible for mediating adaptive angiogenesis seen in the heart after ischemia. The authors find that Akt1, but not Akt2 or Akt3 is responsible.
In an accompanying commentary that discusses all three papers, Brian O'Neill and E. Dale Abel write, "Three separate studies published in this issue of the JCI now provide important new insight into the central role of Akt1 in the regulation of angiogenesis and the maladaptive or deleterious consequences of chronic unregulated Akt activation in the heart." They proceed to discuss the implications of this data.
TITLE 1 Phosphoinositide 3-kinase rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury
AUTHOR CONTACT 1:
Anthony Rosenzweig
Massachusetts General Hospital, Charlestown, MA USA
Phone: 617-726-8286; Fax: 617-724-7387; E-mail: arosenzweig@partners.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=23073
TITLE 2: Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure
AUTHOR CONTACT 2:
Kenneth Walsh
Boston University School of Medicine, Boston, MA USA
Phone: 617-414-2392; Fax: 617-414-2391; E-mail: kxwalsh@bu.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=24682
TITLE 3: Akt1/Protein Kinase B alpha is critical for ischemic and VEGF-mediated angiogenesis
AUTHOR CONTACT 3:
William Sessa
Yale University School of Medicine, New Haven, CT USA
Phone: 203-737-2291; E-mail: william.sessa@yale.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=24726
ACCOMPANYING COMMENTARY:
TITLE: Akt1 in the cardiovascular system: friend or foe?
AUTHOR CONTACT
E. Dale Abel
University of Utah School of Medicine, Salt Lake City, UT USA
Phone: 801-585-0727; Fax: 801-585-0701; E-mail: dale.abel@hmbg.utah.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=25900
Journal
Journal of Clinical Investigation