Abstract 12010: The Pivotal Role of Pentraxin 3, a New Inflammatory Marker, in Hypertensive Failing Heart With Normal Ejection Fraction
Background:Long pentraxin 3 (PTX3) is known to be produced by various types of cell through a lot of inflammatory cytokines such as tumor necrosis factor (TNF)-α. PTX3 is therefore used as an inflammatory marker for acute myocardial infarction and heart failure (HF). However, the precise mechanism of PTX3 in the exacerbation of HF with normal l ejection fraction (HFNEF) remains to be elucidated.
Methods:(1) Dahl salt-sensitive hypertensive rats (DS rats), which are the useful model of HFNEF, fed high-salt (HS) DS rats progressively develop hypertension and exhibit LV hypertrophy (LVH) a, followed by HFNEF. In the present study, we used HS loaded DS rats at the age of 15 and 20 weeks to elucidate the mechanism of transition from hypertensive LVH to HFNEF. (2) We examined the levels of PTX3 at the aortic root and the coronary sinus in HFNEF patients who received CAG during the study period.
Results:(1) 20-week-old HS loaded DS rats were characterized by prominent LVH and marked LV relaxation abnormality but by the preserved LV systolic function. Compared with control DS rats fed low-salt (LS) diet, LV macrophage infiltration and interstitial fibrosis as shown by histological examination were already significantly increased at the stage of LVH, and remained increased up to the stage of HFNEF (P<0.01). In HS-loaded DS rats suffering from HFNEF, immunoreactivity to PTX3 was similarly localized with cardiac interstitial and perivascular fibrosis, and also expressed in infiltrating macrophages. On the other hand, real-time quantitative RT-PCR showed that cardiac TNF-α and PTX3 mRNA expression was not altered at the stage of LVH, but significantly increased at the stage of HFNEF compared with LS control DS rats, while cardiac transforming growth factor (TGF)-β and CTGF, collagen-related cytokines, significantly increased both at LVH and HFNEF stages. (2) In human, plasma levels of PTX3 at coronary sinus were significantly higher than aortic root in patients with HFNEF (n=11, P<0.01), but not different in normal patients (n=20, P=0.22).
Conclusion:PTX3 produced from macrophage, rather than from cardiac fibroblasts, might be associated with transition from LVH to HFNEF. Taken together with human data, PTX3 could be a useful marker for discriminating HFNEF from LVH.
Author Disclosures: E. Yamamoto: None. H. Kusaka: None. Y. Hirata: None. T. Tokitsu: None. D. Sueta: None. K. Fujisue: None. H. Kurokawa: None. K. Sugamura: None. O. Yasuda: None. S.K. Mitsuyama: None. H. Ogawa: None.
- © 2014 by American Heart Association, Inc.