Remodeling of Gap Junctional Coupling in Hypertrophied Right Ventricles of Rats With Monocrotaline-Induced Pulmonary Hypertension

Abstract

The present study investigates the remodeling of gap junctional organization in relation to changes in anisotropic conduction properties in hypertrophied right ventricles (RVs) of rats with monocrotaline (MCT)-induced pulmonary hypertension. In contrast to controls that showed immunolocalization of connexin43 (Cx43) labeling largely confined to the intercalated disks, RV myocytes from MCT-treated rats showed dispersion of Cx43 labeling over the entire cell surface. The disorganization of Cx43 labeling became more pronounced with the progression of hypertrophy. Desmoplakin remained localized to the intercalated disks, as in controls. In RV tissues, the proportion of Cx43 label at the intercalated disk progressively decreased. Quantitative analysis of en face views of intercalated disks revealed a significant decrease in the disk gap junctional density in RV tissues of MCT-treated rats (control, 0.18 versus MCT-treated, 0.14 at 2 weeks; control, 0.16 versus MCT-treated, 0.11 at 4 weeks). Conduction velocity in RVs parallel to the fiber orientation was significantly lower (30.2% [n=9]) in MCT-treated rats at 4 weeks than in control rats, whereas there was no significant difference observed in the conduction velocity across the fiber orientation between control and MCT-treated rats. The anisotropic ratio of MCT-treated rats (1.38+/-0.10) was significantly lower than that of control rats (1.98+/-0.12). These results suggest that RV hypertrophy induced by pressure overload is associated with both disorganization of gap junction distribution and alteration of anisotropic conduction properties.

Myocardial Morphological Characteristics and Proarrhythmic Substrate in the Rat Model of Heart Failure Due to Chronic Volume Overload

“…In a partial contrast with previous studies of connexin43 changes in HF (Dupont et al, 2001;Emdad et al, 2001;Uzzaman et al, 2000), we found only mild difference in total connexin43 levels by immunohistochemistry (but there was over 60% reduction by Western blot), and the changes in localization were also insignificant. Possible reason for this discrepancy can be differences in HF models or methods used.…”

“…Some of the previous studies demonstrated a reduction in connexin43 levels in left ventricles of transplant patients with endstage HF (Dupont et al, 2001). Lateralization of connexin43 from intercalated discs to lateral membrane of myocytes occurs in experimentally induced hypertrophy of right and left ventricle of the rat (Uzzaman et al, 2000;Emdad et al, 2001). Apart from alterations in connexin43 levels, the dephosphorylation of connexin43 was described during several pathological states, including myocardial ischemia (Beardslee et al, 2000;Burstein et al, 2009).…”

Characterization of the ERβ – /–mouse heart

“…One indicator of this stress was the increase in the expression of ␤-MHC, the fetal form of myosin in the mouse (27,28). This is an energy conservation switch as ␤-MHC has a lower ATPase activity.…”

Doppler tissue imaging in assessment of pulmonary hypertension-induced right ventricle dysfunction

“…Recently, it was shown that RV hypertrophy is associated with both disorganization of gap junction distribution and alteration of anisotropic conduction properties (28,29). Consequently, hypertrophic remodeling might induce electromechanical coupling alteration during PHT-induced RV dysfunction (29).…”