Magic™ Anti-Troponin I monoclonal antibody, clone TPC6

Underlying pivotal pathways were identified to reveal potential key genes correlated with postmenopausal osteoporosis (PMOP). The pathways were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) with genes intersection greater than 5 based on gene expression profile data, and the acquired pathways were then transformed to Markov chain (MC). Gibbs sampling was conducted to obtain a new MC. Moreover, the average probabilities of each pathway in normal and PMOP were computed via an MC Monte Carlo (MCMC) algorithm, and differential pathways were identified based on probabilities more than 0.7. In addition, frequencies of appearance of pathway genes were counted via MCMC and the hub genes were achieved with the probabilities of gene expression efficiencies in two states. Judging by the gene intersection more than 5, overall 280 pathways were determined. After Gibbs sampling, 2 differential pathways were obtained on the basis of probabilities more than 0.7. Moreover, the hub genes comprising TNNC1, MYL2, and TTN were achieved according to probabilities more than 0.7. The identified pathways and the three hub genes probably are useful for developing approaches for the diagnosis and treatment of PMOP in future preclinical and clinical applications.

Background Mutations in thin-filament proteins have been linked to hypertrophic cardiomyopathy, but it has never been demonstrated that variants identified in the TNNC1 (gene encoding troponin C) can evoke cardiac remodeling in vivo. The goal of this study was to determine whether TNNC1 can be categorized as an hypertrophic cardiomyopathy susceptibility gene, such that a mouse model can recapitulate the clinical presentation of the proband. Methods and Results The TNNC1-A8V proband diagnosed with severe obstructive hypertrophic cardiomyopathy at 34 years of age exhibited mild-to-moderate thickening in left and right ventricular walls, decreased left ventricular dimensions, left atrial enlargement, and hyperdynamic left ventricular systolic function. Genetically engineered knock-in (KI) mice containing the A8V mutation (heterozygote=KI-TnC-A8V(+/-); homozygote=KI-TnC-A8V(+/+)) were characterized by echocardiography and pressure-volume studies. Three-month-old KI-TnC-A8V(+/+) mice displayed decreased ventricular dimensions, mild diastolic dysfunction, and enhanced systolic function, whereas KI-TnC-A8V(+/-) mice displayed cardiac restriction at 14 months of age. KI hearts exhibited atrial enlargement, papillary muscle hypertrophy, and fibrosis. Liquid chromatography-mass spectroscopy was used to determine incorporation of mutant cardiac troponin C (approximate to 21%) into the KI-TnC-A8V(+/-) cardiac myofilament. Reduced diastolic sarcomeric length, increased shortening, and prolonged Ca2+ and contractile transients were recorded in intact KI-TnC-A8V(+/-) and KI-TnC-A8V(+/+) cardiomyocytes. Ca2+ sensitivity of contraction in skinned fibers increased with mutant gene dose: KI-TnC-A8V(+/+)>KI-TnC-A8V(+/-)>wild-type, whereas KI-TnC-A8V(+/+) relaxed more slowly on flash photolysis of diazo-2. Conclusions The TNNC1-A8V mutant increases the Ca2+-binding affinity of the thin filament and elicits changes in Ca2+ homeostasis and cellular remodeling, which leads to diastolic dysfunction. These in vivo alterations further implicate the role of TNNC1 mutations in the development of cardiomyopathy.