Abstract
Diastolic dysfunction of the heart and decreased compliance of the vasculature and lungs (i.e., increased organ tissue stiffness) are known features of obesity and the metabolic syndrome. Similarly, cardiac diastolic dysfunction is associated with aging. Elevation of the enzyme transglutaminase 2 (TG2) leads to protein cross-linking and enhanced collagen synthesis and participates as a candidate pathway for development of tissue stiffness. With these observations in mind we hypothesized that TG2 may be elevated in tissues of a rat model of obesity/metabolic syndrome (the ZSF 1 rat) and a mouse model of aging, i.e., the senescent SAMP8 mouse. In the experiments reported here, TG2 expression and activity were found for the first time to be spontaneously elevated in organs from both the ZSF1 rat and the SAMP8 mouse. These observations are consistent with a hypothesis that a TG2-related pathway may participate in the known tissue stiffness associated with cardiac diastolic dysfunction in these two rodent models. The potential TG2 pathway needs better correlation with physiologic dysfunction and may eventually provide novel therapeutic insights to improve tissue compliance.
Highlights
It is well known that the pathophysiology and progression of multiple human diseases are associated with tissue stiffness
Consistent with the diabetic nephropathy observed in ZSF1 obese rats, transglutaminase 2 (TG2) levels are increased in kidneys (Figure 1C) and livers (Figure 1D) of this rat model
We have not yet related TG2 activity to tissue compliance, our present in vivo observations with rodent models of metabolic syndrome (ZSF1 obese rats) and aging (SAMP8 mice) are consistent with participation of TG2 in cardiac and lung matrix changes that are associated with tissue stiffness in multiple cardiovascular and pulmonary diseases mediated by these conditions
Summary
It is well known that the pathophysiology and progression of multiple human diseases are associated with tissue stiffness (or loss of compliance). Such disease processes may involve other non-contractile organs such as the kidney and liver, they are most evident in contractile tissues such as heart, lungs, and the vasculature. There has been a gradual accumulation of data that associates TG2 with synthesis and cross-linking of extracellular matrix proteins that produces tissue stiffness (Mosher and Schad, 1979; Orban et al, 2004). Our data indicate for the first-time that metabolic dysfunction and aging are associated with increased TG2 expression and activity in multiple tissues, including heart and lungs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
