Abstract 13108: Disturbance in Cardiac Th1/th2 Cytokine Balance Plays the Pivotal Role in 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 diastolic heart failure (DHF).
Method: (1) To investigate the mechanism underlying the progression of decompensated DHF, we examined time course change of cardiac cytokines of high-salt diet Dahl salt-sensitive hypertensive rats (DS rats), which exhibits compensated LV hypertrophy at the age of 14 weeks, followed by decompensated DHF at the age of 20 weeks. (2) To elucidate the involvement of angiotensin II (Ang II), we examined the effect of candesartan (1mg/kg), an Ang II receptor blocker on high-salt diet DS rats suffering from DHF.
Results: (1) Compared with control DS rats fed low-salt diet, LV macrophage infiltration and interstitial fibrosis as shown by histological examination were already significantly increased at the stage of LV hypertrophy and remained increased up to the stage of 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 proinflammatory and a Th1 cytokine, mRNA expression was not altered at 14 weeks of age, but significantly increased at 20 weeks of age, compared with low-salt diet. 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. (2) Treatment of DS rats suffering from DHF with candesartan significantly ameliorated DHF and survival rate, by improving cardiac macrophage infiltration but not interstitial fibrosis. Moreover, the Ang II blockade by candesartan significantly reduced cardiac TNF-α/IL-6 mRNA ratio but did not normalize the above mentioned fibrosis-related cytokine mRNA expressions in DS rats.
Conclusions: Ang II-induced transition to decompensated DHF in salt-sensitive hypertension might be associated with Th1-dominant response in TH1/Th2 cytokine balance represented by increase in TNF-α/IL-6 ratio.
- © 2012 by American Heart Association, Inc.