NO-cGMP and TNF-alpha counter regulatory system in blood: understanding the mechanisms leading to myocardial dysfunction and failure.
One of the major conceptual advances in the understanding of the pathogenesis of heart failure has been the insight that myocardial dysfunction and heart failure may progress as the result of the sustained over-expression of nitric oxide (NO) metabolites locally and in blood modulated by inducible nitric oxide synthase (iNOS). This by virtue of their deleterious effects is sufficient to contribute to disease progression by provoking left ventricular (LV) remodeling, hypertrophy and progressive LV dysfunction. Recently, tumor necrosis factor-alpha (TNF-alpha) has also been identified in this setting of heart failure. Analogous to the situation with NO, the over-expression of TNF-alpha is sufficient to contribute to disease progression in heart failure phenotype. Although important interactions between TNF-alpha and the NO have been recognized in the cardiovascular system for over a decade, the nature and importance of the interactions between these biologically active molecules in cardiac hypertrophy has become apparent only in the recent times. Therefore, we focused on the prevailing updated evidence which suggests that there is a functionally significant cross-regulation between NO and TNF-alpha signaling in blood thus playing a part in cardiac hypertrophy and failure. The discussions presented here will have a bearing on the therapeutic potential via inhibitors of these pathways in reducing cardiomyocyte hypertrophy and the LV dysfunction.
Elahi
Maqsood
M
Wessex Cardiothoracic Centre, Chalybeate Close, Southampton, SO16 6UY, UK.
Asopa
Sanjay
S
Matata
Bashir
B
D000818:Animals; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism*; D018450:Disease Progression; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006152:Cyclic GMP