Cross-regulation between the renin-angiotensin system and inflammatory mediators in cardiac hypertrophy and failure.
One of the major conceptual advances in our understanding of the pathogenesis of heart failure has been the insight that heart failure may progress as the result of the sustained overexpression of biologically active "neurohormones", such as norepinephrine and angiotensin II, which by virtue of their deleterious effects are sufficient to contribute to disease progression by provoking worsening left ventricular (LV) remodeling and progressive LV dysfunction. Recently, a second class of biologically active molecules, termed cytokines, has also been identified in the setting of heart failure. Analogous to the situation with neurohormones, the overexpression of cytokines is sufficient to contribute to disease progression in heart failure phenotype. Although important interactions between proinflammatory cytokines and the adrenergic system have been recognized in the heart for over a decade, the nature of the important interactions between proinflammatory cytokines and the renin-angiotensin system has become apparent only recently. Accordingly, in the present review, we will discuss the evidence which suggests that there is a functionally significant cross-talk between neurohormonal and inflammatory cytokine signaling in cardiac hypertrophy and failure.
Cardiology Section of the Department of Medicine, Winters Center for Heart Failure Research, Houston VAMC and Baylor College of Medicine, 6565 Fannin, MS 524, Houston, TX 77030, USA.
Kenichi
K
Sekiguchi
Xia
X
Li
Mytsi
M
Coker
Markus
M
Flesch
Philip M
PM
Barger
Natarajan
N
Sivasubramanian
Douglas L
DL
Mann
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II