Oxidative mechanism and homeostasis of proteinase/antiproteinase in congestive heart failure

Takenaka et al. [Takenaka H, Kihara Y, Iwanaga Y, Onozawa Y, Toyokuni S, Kita T. Angiotensin II, oxidative stress, and extracellular matrix degradation during transition to LV failure in rats with hypertension, J Mol Cell Cardiol, 2006; in press] in this issue have shown that during LV failure in hypertension, there is induction of oxidative stress in which p47 and gp91, and glutathione peroxidase are increased via the NFkB pathway oxidative stress which induces the MMP/TIMP axis, leading to cardiac dilation and failure. The ARB ameliorates the CHF by decreasing oxidative stress [Funabiki K, et al., Combined angiotensin receptor blocker and ACE inhibitor on myocardial fibrosis and LV stiffness in dogs with heart failure, Am J Physiol, 2004; 287(6): H2487–92]. This study supports the notion that the inciting oxidative stress activates the matrix degrading proteinase. That disrupts the connective tissue matrix homeostasis in between the myocyte and endothelial cells causing disruption in synchronization in cardiac systolic contraction and diastolic relaxation. The treatment with ARB mitigates this disruption in cardiac synchrony.