Copyright © 2006, European Society of Cardiology
Integrin signalling: The tug-of-war in heart hypertrophy
aDepartment of Genetics, Biology, and Biochemistry, Turin University, Via Santena, 5bis, 10126 Turin, Italy
bDepartment of Angiocardioneurology, I.R.C.C.S. "Neuromed", 86077 Pozzilli (IS), Italy
cExperimental Medicine Research Center, San Giovanni Battista Hospital, 10126 Turin, Italy
dDepartment of Experimental Medicine and Pathology, "La Sapienza" University of Rome, Italy
* Corresponding author. Department of Genetics, Biology, and Biochemistry, Turin University, Via Santena, 5bis, 10126 Turin, Italy. Tel.: +39 011 6705858; fax: +39 011 6705853. Email address: guido.tarone{at}unito.it
The mechanical stress imposed by hemodynamic overload on heart walls is a primary event in triggering the cardiac hypertrophic response. Integrins, a class of membrane receptors, are major players in transmitting the mechanical force across the plasma membrane and sensing the mechanical load in cardiomyocytes. In fact, integrins, together with a number of associated cytoskeletal proteins, connect the sarcomeric contractile apparatus to the extracellular matrix across the plasma membrane and trigger intracellular signaling pathways activating the cardiomyocyte hypertrophy program.
In this review, we will discuss the role of the muscle-specific integrin isoform β1D and of associated proteins such as FAK, melusin, vinculin, zyxin, VASP, and migfilin that are the most upstream elements ("initiators") activated by mechanical strain. These molecules trigger a coordinated downstream signaling cascade involving proteins such as AKT, RAS, and MAPKs that execute the biochemical program leading to cardiomyocyte hypertrophy. Better understanding of the functional role of the initiator elements is of key importance to developing novel strategies to control cardiac hypertrophy and prevent heart failure.
KEYWORDS Cardiac hypertrophy; Integrins; Mechano-transduction; Signal transduction