Religiosity and Excess Weight Among African-American Adolescents: The Jackson Heart KIDS Study.

Recent studies suggest that religion and spirituality can yield health benefits for young African-Americans. We examined the relationship between religious practices, spirituality, and excess weight among African-American adolescents (N = 212) residing in the Deep South. Results from modified Poisson regression analysis indicate that adolescents who prayed daily had a lower prevalence of excess weight (PR 0.77 [95% CI 0.62-0.96]) than those who did not. This relationship was only significant for 12-15 year-old participants in age-stratified analysis. These findings suggest that preventive interventions offered to children and younger adolescents can have implications for weight status across the lifespan.

Associations Among Caregiver Feeding Practices and Blood Pressure in African American Adolescents: The Jackson Heart KIDS Study.

Caregiver feeding practices have been linked to youth health outcomes. The present study examined associations among caregiver feeding practices and blood pressure in 212 African American adolescents via the Child Feeding Practices Questionnaire. Results revealed a positive association between caregivers' concern about their child's weight and diastolic blood pressure, which was more acute for older adolescent boys. Caregivers' perceived responsibility for the quality and quantity of food their child receives was also associated with lower diastolic blood pressure in older adolescent boys. Feeding practices are ideal targets of lifestyle intervention, and health care providers should continue to involve caregivers as adolescents approach adulthood.

Caregiver feeding practices and weight status among African American adolescents: The Jackson Heart KIDS Pilot Study.

Adolescence is a stage in the life course during which youth become more autonomous in their health behaviors. Overweight and obesity during this developmental period are associated with short- and long-term physical and emotional morbidity, and African American youth are at pronounced risk for these health outcomes. The style of parenting employed by caregivers influences health behaviors in children, though the persistence of this influence into adolescence is not clear. This study examined associations among caregiver feeding practices, body mass index z-score (zBMI), and waist circumference (WC) in a cohort of 212 African American adolescents (50.5% girls; Mage=15.16years). Participants were children and grandchildren of individuals enrolled in the Jackson Heart Study, a prospective epidemiologic evaluation of cardiovascular disease among African Americans based in Jackson, Mississippi. Youth zBMI and WC were primary outcomes, and caregivers completed the Child Feeding Questionnaire, an assessment of attitudes, beliefs, and practices related to obesity proneness. Regression analyses revealed that while controlling caregiver feeding practices were associated with zBMI and WC, perceived responsibility for the type and amount of food provided to adolescents was not related to weight status. Among younger adolescents, more oversight of their eating practices was related to higher zBMI. Similarly, boys whose intake of unhealthy foods was restricted were more likely to have higher zBMI and WC. Results suggest that caregiver feeding practices continue to be associated with weight status during adolescence, and underscore the importance of culturally and developmentally appropriate prevention and intervention efforts targeting overweight and obesity.

N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy.

S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca(2+) sensitization and a slowing of cross-bridge kinetics as a result of increased oxidative signaling. Although there is evidence for a role of oxidative stress in disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is not well understood. We investigated whether oxidative myofilament modifications may be in part responsible for diastolic dysfunction in HCM. We administered N-acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic mice expressing a mutant tropomyosin (Tm-E180G) and nontransgenic littermates. Tm-E180G hearts demonstrate a phenotype similar to human HCM. After NAC administration, the morphology and diastolic function of Tm-E180G mice was not significantly different from controls, indicating that NAC had reversed baseline diastolic dysfunction and hypertrophy in our model. NAC administration also increased sarco(endo)plasmic reticulum Ca(2+) ATPase protein expression, reduced extracellular signal-related kinase 1/2 phosphorylation, and normalized phosphorylation of phospholamban, as assessed by Western blot. Detergent-extracted fiber bundles from NAC-administered Tm-E180G mice showed nearly nontransgenic (NTG) myofilament Ca(2+) sensitivity. Additionally, we found that NAC increased tension cost and rate of cross-bridge reattachment. Tm-E180G myofilaments were found to have a significant increase in S-glutathionylation of cMyBP-C, which was returned to NTG levels upon NAC administration. Taken together, our results indicate that oxidative myofilament modifications are an important mediator in diastolic function, and by relieving this modification we were able to reverse established diastolic dysfunction and hypertrophy in HCM.

Novel control of cardiac myofilament response to calcium by S-glutathionylation at specific sites of myosin binding protein C.

Our previous studies demonstrated a relation between glutathionylation of cardiac myosin binding protein C (cMyBP-C) and diastolic dysfunction in a hypertensive mouse model stressed by treatment with salt, deoxycorticosterone acetate, and unilateral nephrectomy. Although these results strongly indicated an important role for S-glutathionylation of myosin binding protein C as a modifier of myofilament function, indirect effects of other post-translational modifications may have occurred. Moreover, we did not determine the sites of thiol modification by glutathionylation. To address these issues, we developed an in vitro method to mimic the in situ S-glutathionylation of myofilament proteins and determined direct functional effects and sites of oxidative modification employing Western blotting and mass spectrometry. We induced glutathionylation in vitro by treatment of isolated myofibrils and detergent extracted fiber bundles (skinned fibers) with oxidized glutathione (GSSG). Immuno-blotting results revealed increased glutathionylation with GSSG treatment of a protein band around 140 kDa. Using tandem mass spectrometry, we identified the 140 kDa band as cMyBP-C and determined the sites of glutathionylation to be at cysteines 655, 479, and 627. Determination of the relation between Ca(2+)-activation of myofibrillar acto-myosin ATPase rate demonstrated an increased Ca(2+)-sensitivity induced by the S-glutathionylation. Force generating skinned fiber bundles also showed an increase in Ca-sensitivity when treated with oxidized glutathione, which was reversed with the reducing agent, dithiothreitol (DTT). Our data demonstrate that a specific and direct effect of S-glutathionylation of myosin binding protein C is a significant increase in myofilament Ca(2+)-sensitivity. Our data also provide new insights into the functional significance of oxidative modification of myosin binding protein C and the potential role of domains not previously considered to be functionally significant as controllers of myofilament Ca(2+)-responsiveness and dynamics.

Decreasing tropomyosin phosphorylation rescues tropomyosin-induced familial hypertrophic cardiomyopathy.

Studies indicate that tropomyosin (Tm) phosphorylation status varies in different mouse models of cardiac disease. Investigation of basal and acute cardiac function utilizing a mouse model expressing an α-Tm protein that cannot be phosphorylated (S283A) shows a compensated hypertrophic phenotype with significant increases in SERCA2a expression and phosphorylation of phospholamban Ser-16 (Schulz, E. M., Correll, R. N., Sheikh, H. N., Lofrano-Alves, M. S., Engel, P. L., Newman, G., Schultz Jel, J., Molkentin, J. D., Wolska, B. M., Solaro, R. J., and Wieczorek, D. F. (2012) J. Biol. Chem. 287, 44478-44489). With these results, we hypothesized that decreasing α-Tm phosphorylation may be beneficial in the context of a chronic, intrinsic stressor. To test this hypothesis, we utilized the familial hypertrophic cardiomyopathy (FHC) α-Tm E180G model (Prabhakar, R., Boivin, G. P., Grupp, I. L., Hoit, B., Arteaga, G., Solaro, R. J., and Wieczorek, D. F. (2001) J. Mol. Cell. Cardiol. 33, 1815-1828). These FHC hearts are characterized by increased heart:body weight ratios, fibrosis, increased myofilament Ca(2+) sensitivity, and contractile defects. The FHC mice die by 6-8 months of age. We generated mice expressing both the E180G and S283A mutations and found that the hypertrophic phenotype was rescued in the α-Tm E180G/S283A double mutant transgenic animals; these mice exhibited no signs of cardiac hypertrophy and displayed improved cardiac function. These double mutant transgenic hearts showed increased phosphorylation of phospholamban Ser-16 and Thr-17 compared with the α-Tm E180G mice. This is the first study to demonstrate that decreasing phosphorylation of tropomyosin can rescue a hypertrophic cardiomyopathic phenotype.

Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia.

Changes in metabolic and myofilament phenotypes coincide in developing hearts. Posttranslational modification of sarcomere proteins influences contractility, affecting the energetic cost of contraction. However, metabolic adaptations to sarcomeric phenotypes are not well understood, particularly during pathophysiological stress. This study explored metabolic adaptations to expression of the fetal, slow skeletal muscle troponin I (ssTnI). Hearts expressing ssTnI exhibited no significant ATP loss during 5 min of global ischemia, while non-transgenic littermates (NTG) showed continual ATP loss. At 7 min ischemia TG-ssTnI hearts retained 80±12% of ATP versus 49±6% in NTG (P<0.05). Hearts expressing ssTnI also had increased AMPK phosphorylation. The mechanism of ATP preservation was augmented glycolysis. Glycolytic end products (lactate and alanine) were 38% higher in TG-ssTnI than NTG at 2 min and 27% higher at 5 min. This additional glycolysis was supported exclusively by exogenous glucose, and not glycogen. Thus, expression of a fetal myofilament protein in adult mouse hearts induced elevated anaerobic ATP production during ischemia via metabolic adaptations consistent with the resistance to hypoxia of fetal hearts. The general findings hold important relevance to both our current understanding of the association between metabolic and contractile phenotypes and the potential for invoking cardioprotective mechanisms against ischemic stress. This article is part of a Special Issue entitled "Possible Editorial".