Abstract 3397: The Long Pentraxin PTX3 Exacerbates Pressure Overload-induced Left Ventricular Dysfunction
Background: Left ventricular hypertrophy is enhanced by inflammatory states and stimulation of various cytokines. PTX3 is rapidly produced in response to inflammatory signals and plasma PTX3 levels are increased in patients with heart failure. The purpose of this study was to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction.
Methods and Results: Expression of PTX3 was increased in the heart by pressure overload after the transverse aortic contraction (TAC) operation. To evaluate the potential mechanism of PTX3 to LV dysfunction, we used two different genotypes of mice, PTX3 systemic knock out (PTX3-KO) mice and PTX3 cardiac specific overexpression (PTX3-TG) mice. Both types of mice and respective wild type mice were subjected to TAC or sham operation. Activation of extracellular signal-regulated kinase was attenuated in PTX3-KO mice, but enhanced in PTX3-TG mice after TAC. Interleukin-6 production was lower in PTX3-KO, and that was higher in PTX3-TG mice. The ratio of heart weight to body weight was significantly increased after TAC operation, and this increase was significantly lower in PTX3-KO mice and higher in PTX3-TG mice than in respective WT mice. Adverse remodeling with left ventricular dysfunction and interstitial fibrosis demonstrated by echocardiographic measurement and microscopic analysis were suppressed in PTX3-KO mice, and that were accelerated in PTX3-TG mice. Left ventricular end-diastolic pressure were lower in PTX3-KO mice, and that were higher in PTX3-TG mice.
Conclusion: The local inflammatory mediator PTX3 has an accelerated effect of hypertrophy and ventricular dysfunction by increase of afterload.