The central importance of the cytoskeleton for increased cell stiffness in cardiovascular disease. Focus on "Diabetes increases stiffness of live cardiomyocytes measured by atomic force microscopy nanoindentation".

Abstract

ATOMIC FORCE MICROSCOPY (AFM) is proving to be a very useful tool for probing nanoscale and microscale mechanical properties and behavior of cells. A cursory search of the literature reveals that the use of the technique to study various characteristics of myocardial cells dates back to the mid-1990s (2, 7). Perhaps more revealing is its ever-more-frequent application to the study of myocardial contractile function and dysfunction (5, 9, 10). In this issue of American Journal of Physiology-Cell Physiology, Benech et al. (1) are, to my knowledge, the first to use AFM to study left ventricular myocardial cells in diabetes mellitus to gain a deeper understanding of the mechanical and functional events that may underlie heart failure in that disease. Importantly, heart failure is a complication that is frequently associated with the diabetic state and is likely to be of increasing importance with the increased prevalence of type 2 diabetes and insulin-resistant states. Several striking observations were made in the elegant study of Benech et al. (1). First, they observe that, in their streptozotocin model of diabetes, myocytes from the diabetic animals are stiffer than those from control mice. In addition, the increase in stiffness appears associated with decreased expression of the sarco/endoplasmic reticulum Ca 2 -ATPase 2 (SERCA2) and a disordered cytoskeletal organization within the myocytes. The latter changes appeared to strongly influence the actin cytoskeleton. Although the reduced SERCA2 expression would make one suspect that a component of the increased stiffness in the diabetic animals was related to intracellular Ca 2 , the increase in stiffness was apparent even when intracellular Ca 2 was reduced to low levels in a near-Ca 2 -free buffer. Again, this appears to strongly indicate that