Stretch-activated pathways and left ventricular remodeling.
Stretch of cardiomyocytes in vivo occurs in response to a number of stimuli, including pressure or volume overload, but it is most clearly seen following relatively large, acute myocardial infarctions. It is in this setting that stretch is most clearly related to the pathogenesis of heart failure. Stretch of the remote, noninfacted myocardium leads to the activation of a large number of cellular signal transduction pathways, which sets into motion a series of what are designed to be compensatory responses to the increased wall stress on the surviving myocardium. Herein, we will discuss the cellular pathways activated by cell stretch, which appear to trigger the initial steps in the pathogenesis of ventricular dilatation following myocardial infarction. We will discuss what is known of the "stretch sensors," which convert the mechanical stimulus into molecular signals. I will then introduce the specific cellular signaling pathways activated by stretch and discuss the evidence for their involvement in remodeling. Since many of these pathways will be covered in more detail in specific sections to follow, this will serve as an introduction to stretch-activated signaling. Finally, we will briefly examine later phases of the response, including advanced heart failure. The goal is to identify molecular modulators that might serve as targets for pharmacologic or molecular intervention.
Force
Thomas
T
Molecular Cardiology Research Institute, New England Medical Center, Boston, MA 02111, USA.
Michael
Ashour
A
Kilter
Heiko
H
Haq
Syed
S
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D019332:Endothelin-1 / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D016023:Integrins / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000502:physiology; D015398:Signal Transduction; D020257:Ventricular Remodeling
D019332:Endothelin-1; D016023:Integrins; D015850:Interleukin-6; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D019204:GTP-Binding Proteins