Cardiac volume overload rapidly induces oxidative stress-mediated myocyte apoptosis and hypertrophy

Abstract

Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in vitro. We investigated the role of oxidative stress in the initial phases of cardiac remodeling induced in an animal model by volume overload. As plausible candidates for a connection between oxidative stress and cardiomyocyte apoptosis or hypertrophy, we explored the behaviour of two MAPKs, specifically JNK and ERK. At 48 h of overload, the greatest increase in oxidative stress coincided with a peak of cardiomyocyte apoptosis. This was possibly induced through the mitochondrial metabolism, as evidenced by the release of cytochrome c and a significant increase in the active forms of caspase-9 and -3, but not caspase-8. Oxidative stress markers significantly decreased at 96 h of overload, combined with a marked attenuation of apoptosis and the appearance of hypertrophy. The highest levels of JNK and the lowest levels of ERK phosphorylation were observed at 48 h of overload. Conversely, a sharp increase in ERK phosphorylation was detected at 96 h of overload coinciding with the hypertrophic response. Together these results show that oxidative stress is an early and transient event in myocardial volume overload. They suggest that oxidative stress mediates amplitude dependent apoptotic and hypertrophic responses in cardiomyocytes through the selective activation of, respectively, JNK and ERK.

Cardiomyocyte apoptosis in the right auricle of patients with ostium secundum atrial septal defect diseases

“…Oxidative stress has been found to link to the occurrence of cardiomyocyte apoptosis in volume overloaded animal hearts (Fiorillo et al, 2005). Hanna and colleagues (Hanna et al, 2004) also reported apoptotic cells increased transiently in left atrial tissues after 24 h tachypacing in dogs, suggesting the possibility that apoptosis originates due to increased stresses which result from an increased volume load of the right heart.…”

Upregulation of the kappa opioidergic system in left ventricular rat myocardium in response to volume overload

“…On the contrary, U50,488H has been shown to increase myofilament responsiveness to calcium [48] and its cardioprotective effects were abolished by the free radical scavenger N-acetylcysteine. Interestingly, an increase in oxidative stress and a reduction in antioxidants have also been associated with heart failure [49], in particular cardiac volume overload [50]. In this context it is interesting that-for the first time-we were able to detect KOR immunoreactivity inside mitochondria of left ventricular cardiomyocytes.…”

Cardioprotective Role of Sodium Thiosulfate on Chronic Heart Failure by Modulating Endogenous H₂S Generation

“…This suggested the possible role of STS in TIMP-1 and AC VI regulation in the failing heart. Oxidative stress due to volume overload has been implicated in the pathogenesis of cardiac disorders [37] . Increased cardiac filling pressures, reduced cardiac output, excessive peripheral vasoconstriction are the established hallmarks of heart failure that result in volume overload [38,39] .…”