doi: 10.1161/01.RES.0000223522.47948.16
© 2006 American Heart Association, Inc.
Editorials |
Viewing a Stressful Episode of ER
Is ATF6 the Triage Nurse?
From the Center for Cardiovascular Translational Biomedicine, Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City.
Correspondence to Ivor J. Benjamin MD, FAHA, Center for Cardiovascular Translational Biomedicine, Division of Cardiology, University of Utah Health Sciences Center, 30 North 1900 East, Salt Lake City, UT 84132. E-mail Ivor.Benjamin@hsc.utah.edu
See related article, pages 1186–1193
Key Words: ER stress • ischemia • transcriptional regulation • HSPs
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
How cardiac cells sense, respond, and adapt to acute and chronic changes of their metabolic and environmental milieu remain among the most enigmatic and fundamental questions in contemporary cardiovascular biology and medicine. With more than 700 000 deaths and 6 million hospital discharges annually in the U.S., ischemic heart disease remains a major public health problem. If prompt therapy is delayed, myocardial injury from depletion of high-energy phosphates from inhibition of oxidative phosphorylation is inevitable. Ischemia/reperfusion (I/R) also unleashes a cascade of cellular and molecular events whose sequalae may sustain organ function at diminished capacity but, beyond a critical balance, threatens the organism’s survival. Reactive oxygen and nitrogen species (ROS; RNS), released from the mitochondria and other sources, alter the tertiary and quaternary structures of proteins, exposing their hydrophobic residues to allow conformational tendencies toward protein misfolding and aggregation.1 Nevertheless, highly sophisticated schemes equipped with molecular sensors, rapid response pathways, and adaptor mechanisms have evolved to mitigate the accumulation of unfolded proteins in a compartment specific manner, principally the cytoplasm and endoplasmic reticulum (ER). Although the cardiovascular field has paid considerably more attention to the cytoprotective mechanisms of heat shock proteins in response to I/R, termed the "classical" heat shock response, a parallel series of events has been unfolding at a breathtaking pace in the ER, with arguably considerable excitement to warrant a sneak preview of the article published in this issue of Circulation Research.
To place into perspective the current buzz being garnered by the ER requires a
Related Article:
Circ. Res. 2006 98: 1186-1193.