Response of caspase-independent apoptotic factors to high salt diet-induced heart failure

Abstract

The role of caspase-independent apoptotic events in heart failure is largely unknown. The present study examined the response of apoptotic factors, which can function independently of caspase machinery including AIF, EndoG, and HtrA2/Omi to high salt diet-induced pathologic heart failure and exercise-induced physiologic cardiac hypertrophy. Following ~4 months of a daily diet containing 6% salt, animals developed clinical evidence of heart failure accompanied by changes in AIF, EndoG, and HtrA2/Omi. Assessment of the mitochondria-free cytosolic fraction revealed cytosolic accumulations of AIF and processed HtrA2/Omi in the failed ventricle muscles. The subcellular translocation of AIF from mitochondria to cytosol and nuclei was supported by immunofluorescent analysis using confocal microscopy. However, according to our RT-PCR analyses, AIF and EndoG mRNA were decreased, rather than elevated, in the failed heart relative to control heart. No difference in any of the measured parameters of AIF, EndoG, and HtrA2/Omi was found in the ventricle muscle of either exercise-trained or 6 weeks high salt diet fed animals compared to controls. These findings are consistent with the hypothesis that caspase-independent events are involved in cardiac apoptosis during the late remodeling stage of pathologic heart failure.

Deletion of Ptpn11 (Shp2) in Cardiomyocytes Causes Dilated Cardiomyopathy via Effects on the Extracellular Signal–Regulated Kinase/Mitogen-Activated Protein Kinase and RhoA Signaling Pathways

“…Sections were stained with hematoxylin and eosin or reticulin at the Rodent Histopathology Core at Harvard Medical School (Boston, Mass). Apoptosis was assessed in paraffin-embedded heart slices by immunohistochemistry using cleaved caspase-3 antibodies or by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, as previously described, 28 at the Brigham and Women's Hospital Histopathology Core Facility (Boston, Mass). Control immunohistochemistry for Shp2 expression was performed with a commercial polyclonal Shp2 antibody (C-18; Santa Cruz Biotechnology Inc, Santa Cruz, Calif).…”

Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway

“…Transthoracic echocardiography was conducted before the doxorubicin injection and after the 4-day experimental period to assess the cardiac structure and function. Echocardiography was performed according to a previously described protocol (45). Mice were anesthetized with an ip injection of ketamine HCl, and the ventral thorax was shaved and covered with ultrasonic transmission gel.…”

Exaggerated hypertensive response to combretastatin A-4 phosphate in hypertensive rats: Effective pharmacological inhibition by diltiazem

“…Pathological cardiac hypertrophy was generated in female Dahl salt sensitive (DSS) rats (Harlan Sprague Dawley, Indianapolis, IN) as described previously by our laboratory [21][22][23]. Control group was age-matched DSS females rats fed normal rat chow.…”

“…The DSS rat is previously characterized HS diet-induced model of hypertension and heart failure [21][22][23]. At the age of 6 weeks MAP of DSS rats averaged 79 mmHg.…”

“…1A). In addition, by the age of 12 weeks, we have previously demonstrated that animals fed the HS diet develop significant cardiac hypertrophy [22][23][24]. We first tested the effect of CA4P at different time points to determine the duration of HS diet needed to observe a potential pathological response to CA4P-one that might mimic what is observed in a clinical setting with patients receiving CA4P.…”