Biomarkers for the identification of cardiac fibroblast and myofibroblast cells.

Experimental research has recognized the importance of cardiac fibroblast and myofibroblast cells in heart repair and function. In a normal healthy heart, the cardiac fibroblast plays a central role in the structural, electrical, and chemical aspects within the heart. Interestingly, the transformation of cardiac fibroblast cells to cardiac myofibroblast cells is suspected to play a vital part in the development of heart failure. The ability to differentiate between the two cells types has been a challenge. Myofibroblast cells are only expressed in the stressed or failing heart, so a better understanding of cell function may identify therapies that aid repair of the damaged heart. This paper will provide an outline of what is currently known about cardiac fibroblasts and myofibroblasts, the physiological and pathological roles within the heart, and causes for the transition of fibroblasts into myoblasts. We also reviewed the potential markers available for characterizing these cells and found that there is no single-cell specific marker that delineates fibroblast or myofibroblast cells. To characterize the cells of fibroblast origin, vimentin is commonly used. Cardiac fibroblasts can be identified using discoidin domain receptor 2 (DDR2) while α-smooth muscle actin is used to distinguish myofibroblasts. A known cytokine TGF-ß1 is well established to cause the transformation of cardiac fibroblasts to myofibroblasts. This review will also discuss clinical treatments that inhibit or reduce the actions of TGF-ß1 and its contribution to cardiac fibrosis and heart failure.

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection.

Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-ß-cyclodextrin (MßCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02-1.0 mM MßCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MßCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10-30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 µM MßCD, whereas SLP was more robust and only inhibited with ≥200 µM MßCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression.

Increased release of serotonin from rat primary isolated adult cardiac myofibroblasts.

Elevated blood serotonin levels have been observed in patients with heart failure and serotonin has a role in pathological cardiac function. The serotonin receptor system was examined in adult rat isolated cardiac fibroblast and myofibroblast cells. This is one of the first studies that has investigated serotonin receptors and other proteins involved in the serotonin receptor system in rat cardiac fibroblast and myofibroblast cells. Rat primary cardiac fibroblasts were isolated and transformed into myofibroblasts using 5 ng/ml TGF-ß1. Transformation of cells to myofibroblasts was confirmed with the presence of α-smooth muscle actin using Western blot. Serotonin metabolism and receptor protein expression was assessed using Western blot techniques and serotonin levels measured using ELISA. The 5-HT1A, 5-HT2A and 5-HT2B receptors were found to be present in both rat cardiac fibroblasts and myofibroblast cells, however no significance in protein expression between the two cell types was found (P > 0.05). In this study a significant increase in the serotonin transporter (SERT), tryptophan hydroxylase 1 and extracellular serotonin levels was observed in rat cardiac myofibroblasts when compared to fibroblasts (P < 0.05). These results suggest that serotonin levels may rise in parallel with cardiac myofibroblast populations and contribute to the pathogenesis of heart failure via serotonin receptors.

The influence of family socioeconomic status on toothbrushing practices in Australian children.

OBJECTIVE: To assess the relationship between toothbrushing behavior and socio-demographic characteristics in Australian children. METHODS: Data were collected through the 2012-2014 Australian National Child Oral Health Survey (NCOHS). NCOHS was a cross-sectional survey of representative school children aged 5-14 years of Australia with a total sample size of 24,664 children. RESULTS: Two-thirds (69%) of Australian children brushed twice or more times a day and the mean age of starting toothbrushing with fluoridated toothpaste was 24 months. Males were less consistent with toothbrushing than females (OR = 0.85; 95% CI: 0.74-0.97) and the likelihood of brushing twice or more a day improved with the increase in age (OR = 1.05; 95% CI: 1.02-1.08). Children with university educated (OR = 1.80; 95% CI: 1.44-2.26), vocational trained parents'/guardians' (OR = 1.45, 95% CI 1.11-1.90), living in families with an income of >AU$120,000 (OR = 1.42; 95% CI: 1.08-1.89) and having an overseas born parent (OR = 1.30; 95% CI: 1.07-1.58) were more likely to brush their teeth twice or more a day than their comparative counterparts. Children in households with two children (OR = 1.33; 95% CI: 1.07-1.64) were more likely to brush twice or more than single-child households. Children with a health welfare card tended to delay the start of toothbrushing by 1.4 months in comparison to those without a welfare card. Children with one of the caregivers born overseas started brushing later than those with Australia born caregivers (B = 1.04; SE = 0.46). Children living in high income and educated families and households with two or more children tended to start toothbrushing at an earlier age. CONCLUSIONS: Several family socio-demographic factors influenced toothbrushing habits in Australian children.