Abstract 19398: Diastolic Dysfunction and Deposition of Fibrosis in Pressure Overloaded Hearts is Dependent on Pentraxin3
On the basis of the underlying pathophysiology, it is possible to distinguish two major forms of heart failure (HF): HF owing to reduced left ventricular (LV) systolic function and HF owing to LV diastolic dysfunction. In both cases, chronic remodeling processes in the myocardium antedate overt HF by many years. Inflammation has a pivotal role in cardiac remodeling, and circulating markers of systemic inflammation are independently associated with risk of developing HF and with prognosis after onset. However, the pathophysiological role of many inflammatory biomarkers in HF is poorly understood. In this context, the relationship between circulating levels of pentraxin 3 (PTX3), a novel marker of inflammation, and the presence of diastolic dysfunction and/or overt HF has been emerging. PTX3 belongs to pentraxins, members of a superfamily of multimeric pattern-recognition proteins that can be short (such as CRP) or long (the prototype of this group being PTX3), with important roles at the interface of innate immune response, inflammation, and extracellular matrix remodeling. To dissect the pathophysiological role of PTX3 in the two forms of HF, we subjected mice with a genetic ablation for PTX3 to chronic pressure overload. Both echocardiographic analysis and PV loops revealed an early and sustained protection from LV diastolic dysfunction. As regard the process of cardiac remodeling to pressure overload, absence of PTX3 resulted in reduced recruitment of monocyte and deposition of fibrotic tissue. The systolic function was not affected by the absence of PTX3 and both WT and KO mice developed a comparable systolic dysfunction over time. In conclusion our data fully support the clinical association among PTX3 levels and the presence of diastolic dysfunction and candidate this molecular target as a novel therapeutic approach for HF owing to LV diastolic dysfunction.
- © 2012 by American Heart Association, Inc.