Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts

In response to stretch, cardiac tissue produces natriuretic peptides, which have been suggested to have beneficial effects in heart failure patients. In the present study, we explored the mechanism of stretch-induced brain natriuretic peptide (Nppb) expression in cardiac fibroblasts. Primary adult rat cardiac fibroblasts subjected to 4 h or 24 h of cyclic stretch (10% 1 Hz) showed a 6.6-fold or 3.2-fold (p 20-fold higher in cardiomyocytes than in cardiac fibroblasts, indicating that cardiac fibroblasts were not the main source of Nppb in the healthy heart. Yoda1, an agonist of the Piezo1 mechanosensitive ion channel, increased Nppb expression 2.1-fold (p < 0.05) and significantly induced other extracellular matrix (ECM) remodeling genes. Silencing of Piezo1 reduced the stretch-induced Nppb and Tgfb1 expression in cardiac fibroblasts. In conclusion, our study identifies Piezo1 as mediator of stretch-induced Nppb expression, as well as other remodeling genes, in cardiac fibroblasts

Heritability of objectively assessed and self-reported sedentary behavior

Understanding the sources of the large individual differences in sedentary behavior is of great importance as this behavior is associated with pre-mature mortality and non-communicable diseases. Here, we report on the contribution of genetic and environmental factors to the variation in objectively assessed (accelerometer) sedentary behavior and self-reported sitting and their shared genetic basis. In addition, the overlap of the genetic risk factors influencing sedentary time and moderate-to-vigorous physical activity (MVPA) was estimated. A sample of 800 individuals (twins and their siblings) was equipped with an Actigraph accelerometer for 7 days and reported on their sitting time and time spent on MVPA on those days using the IPAQ-SF. Genetic factors explained 56% (CI: 44%, 65%) of the individual differences in objective sedentary behavior (Actigraph) and 26% (CI: 0%, 51%) of the individual differences in self-reported sedentary behavior (IPAQ-SF). A modest correlation (0.33) was found between these measures, which was for 45% accounted for by genetic influences. The genetic correlation was 0.49 reflecting a partly overlapping set of genes that influenced both measurements. A modest correlation (−0.27) between Actigraph-derived sedentary time and MVPA was found, which was 13% accounted for by genetic effects. The genetic correlation was −0.31, indicating that there are overlapping genetic variants that increase sedentary time and decrease MVPA or vice versa. To conclude, more than half of the individual differences in objective sedentary time could be attributed to genetic differences, while for self-reported sitting this was much lower. In addition, using objective measurements, this study confirms that sedentary time is not simply the inverse of MVPA. Future studies are needed to understand the pathways translating genomic variation into variation in these behaviors and how this knowledge might feed into the development of health promotion interventions