Increased Expression of Interleukin-1β and Monocyte Chemotactic and Activating Factor/Monocyte Chemoattractant Protein-1 in the Hypertrophied and Failing Heart With Pressure Overload

Abstract

Studies on the effects of proinflammatory cytokines on the heart suggest that they play some roles in the pathogenesis of congestive heart failure (CHF). To determine the involvement of proinflammatory cytokine in cardiac hypertrophy and CHF induced by mechanical overload, we investigated the expression of interleukin (IL)-1 beta and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the left ventricle (LV) of Dahl salt-sensitive (DS) rats that showed hypertrophy of the LV induced by hypertension and subsequently developed CHF. The IL-1 beta mRNA content in the LV of DS rats increased 3.9-fold when LV hypertrophy developed, and the increase reached 6.2-fold at the CHF stage compared with that of age-matched Dahl salt-resistant (DR) rats. The amount of IL-1 beta in the LV was positively correlated with the LV weight/body weight ratio. Most of the IL-1 beta immunoreactivity was localized in the endothelial cells and interstitial macrophages. The mRNA levels of MCAF in the LV increased 3.6-fold at 11 weeks and reached 4.8-fold at the CHF stage relative to the age-matched DR rats. MCAF protein was localized to the endothelial cells and interstitial macrophages. In DS rats, the number of interstitial macrophages increased diffusely throughout the LV. We suggest that increased chemokine expression, macrophage infiltration, and proinflammatory cytokine expression play some role in the pathogenesis of cardiac hypertrophy and failure induced by chronic mechanical overload.

Monocyte Chemoattractant Protein-1 is Upregulated in Rats With Volume-Overload Congestive Heart Failure

“…23 An earlier report on MCP-1 expression in a hypertensive model of heart failure in the rat reported that MCP-1 expression was confined primarily to endothelial cells and infiltrating cells. 11 The discrepancy with our results may be due to the underlying cause of cardiomyopathy in the 2 different models.…”

“…10 Pressure overload-induced heart failure in hypertensive animals led to induction of MCP-1. 11 To date, the contribution of MCP-1 to the syndrome of heart failure is attributed solely to its potent chemoattractant properties on monocytes, the presence of which has been documented in cardiac specimens of heart failure. Interestingly, angiotensin II (Ang II), which plays a dominant role in the pathogenesis of CHF, also induces MCP-1 gene expression in vivo and in vitro.…”

CXCR4 modulates contractility in adult cardiac myocytes

“…This class of receptors is present on the myocardium and vascular smooth muscle cell types and is capable of mediating important biological processes in a manner that is independent of inflammatory cells [34]. Recently, several studies have demonstrated that circulating chemokine levels, including that of CXCL12, are elevated in animals and humans with cardiac dysfunction [35][36][37]. Therefore, chemokines have been proposed as mediators of cardiac dysfunction.…”

Pioglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Attenuates Myocardial Ischemia/Reperfusion Injury in a Rat Model

“…The results of our study demonstrate that pioglitazone has inhibitory effects on the inflammatory reaction associated with MI/R injury and that pioglitazone decreases the extent of myocardial injury in a rat model. The important role played by MCP-1 in inflammatory and immune cardiovascular disorders has become increasingly apparent (Behr et al, 2000;Shioi et al, 1997). Recent studies from our laboratories have shown that plasma concentrations of MCP-1 are increased in the early phase of human acute myocardial infarction and that an antibody against MCP-1 reduces myocardial infarct size in rats subjected to MI/R (Ono et al, 1999).…”