Abstract 12007: Cardiac Th1/Th2 Cytokine Imbalance Was Closely Associated With the Transition From Left Ventricular Hypertrophy to Diastolic Heart Failure in Salt-Sensitive Hypertensive Rats
Background: Although cardiac inflammation and fibrosis are closely associated with the progression of cardiac remodeling, little is known about the relative role of inflammation- and fibrosis-related cytokines in the pathophysiology during the transition from left ventricular (LV) hypertrophy to cardiac diastolic heart failure (DHF).
Method:(1) To investigate the mechanism underlying the progression of decompensated cardiac DHF, we examined time-course change of cardiac cytokines of high-salt (HS) diet Dahl salt-sensitive hypertensive rats (DS rats), which exhibits compensated LV hypertrophy (LVH) at the age of 14 weeks, followed by decompensated cardiac DHF at the age of 20 weeks. (2) To elucidate the involvement of Th1/Th2 cytokine imbalance, we examined the effect of interleukin 6 (IL-6) administration (5.6 ug/kg BW i.p.) twice a week to HS-diet DS rats with LVH for 4 weeks (from 14 to 18 week-old).
Results:(1) Compared to 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 cardiac DHF, being accompanied by the increase in cardiac transforming growth factor (TGF)-β, connective tissue growth factor (CTGF), collagen I and collagen III mRNA expression both at 14 and 20 weeks of age. On the other hand, cardiac tumor necrosis factor (TNF)-α, a typical pro-inflammatory and a Th1 cytokine, mRNA expression was not altered at 14 weeks of age, but significantly increased at 20 weeks of age, compared to LS-diet DS rats. Furthermore, cardiac IL-6, a pleiotropic and a Th2 cytokine, mRNA expression tended to increase at 14 weeks of age, but inversely decreased at 20 weeks of age of DS rats. These data suggested that increased TNF-α/IL-6 ratio could be associated with the development of DHF. (2) Improvement of Th1/Th2 cytokine imbalance by IL-6 administration significantly ameliorated LV weight of HS-diet DS rats at decompensated DHF stage.
Conclusions:Transition from LVH to DHF in salt-sensitive hypertension might be directly associated with Th1-dominant response in Th1/Th2 cytokine imbalance represented by increase in TNF-α/IL-6 ratio.
Author Disclosures: E. Yamamoto: None. H. Kusaka: None. Y. Hirata: None. T. Tokitsu: None. K. Sugamura: None. O. Yasuda: None. S. Sugiyama: None. S.K. Mitsuyama: None. H. Ogawa: None.
- © 2014 by American Heart Association, Inc.