Cardiomyocyte ZKSCAN3 regulates remodeling following pressure-overload.

Autophagy is important for protein and organelle quality control. Growing evidence demonstrates that autophagy is tightly controlled by transcriptional mechanisms, including repression by zinc finger containing KRAB and SCAN domains 3 (ZKSCAN3). We hypothesize that cardiomyocyte-specific ZKSCAN3 knockout (Z3K) disrupts autophagy activation and repression balance and exacerbates cardiac pressure-overload-induced remodeling following transverse aortic constriction (TAC). Indeed, Z3K mice had an enhanced mortality compared to control (Con) mice following TAC. Z3K-TAC mice that survived exhibited a lower body weight compared to Z3K-Sham. Although both Con and Z3K mice exhibited cardiac hypertrophy after TAC, Z3K mice exhibited TAC-induced increase of left ventricular posterior wall thickness at end diastole (LVPWd). Conversely, Con-TAC mice exhibited decreases in PWT%, fractional shortening (FS%), and ejection fraction (EF%). Autophagy genes (Tfeb, Lc3b, and Ctsd) were decreased by the loss of ZKSCAN3. TAC suppressed Zkscan3, Tfeb, Lc3b, and Ctsd in Con mice, but not in Z3K. The Myh6/Myh7 ratio, which is related to cardiac remodeling, was decreased by the loss of ZKSCAN3. Although Ppargc1a mRNA and citrate synthase activities were decreased by TAC in both genotypes, mitochondrial electron transport chain activity did not change. Bi-variant analyses show that while in Con-Sham, the levels of autophagy and cardiac remodeling mRNAs form a strong correlation network, such was disrupted in Con-TAC, Z3K-Sham, and Z3K-TAC. Ppargc1a also forms different links in Con-sham, Con-TAC, Z3K-Sham, and Z3K-TAC. We conclude that ZKSCAN3 in cardiomyocytes reprograms autophagy and cardiac remodeling gene transcription, and their relationships with mitochondrial activities in response to TAC-induced pressure overload.

Low-Temperature Plasmas Improving Chemical and Cellular Properties of Poly (Ether Ether Ketone) Biomaterial for Biomineralization.

Osteoblastic and chemical responses to Poly (ether ether ketone) (PEEK) material have been improved using a variety of low-temperature plasmas (LTPs). Surface chemical properties are modified, and can be used, using low-temperature plasma (LTP) treatments which change surface functional groups. These functional groups increase biomineralization, in simulated body fluid conditions, and cellular viability. PEEK scaffolds were treated, with a variety of LTPs, incubated in simulated body fluids, and then analyzed using multiple techniques. First, scanning electron microscopy (SEM) showed morphological changes in the biomineralization for all samples. Calcein staining, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) confirmed that all low-temperature plasma-treated groups showed higher levels of biomineralization than the control group. MTT cell viability assays showed LTP-treated groups had increased cell viability in comparison to non-LTP-treated controls. PEEK treated with triethyl phosphate plasma (TEP) showed higher levels of cellular viability at 82.91% ± 5.00 (n = 6) and mineralization. These were significantly different to both the methyl methacrylate (MMA) 77.38% ± 1.27, ethylene diamine (EDA) 64.75% ± 6.43 plasma-treated PEEK groups, and the control, non-plasma-treated group 58.80 ± 2.84. FTIR showed higher levels of carbonate and phosphate formation on the TEP-treated PEEK than the other samples; however, calcein staining fluorescence of MMA and TEP-treated PEEK had the highest levels of biomineralization measured by pixel intensity quantification of 101.17 ± 4.63 and 96.35 ± 3.58, respectively, while EDA and control PEEK samples were 89.53 ± 1.74 and 90.49 ± 2.33, respectively. Comparing different LTPs, we showed that modified surface chemistry has quantitatively measurable effects that are favorable to the cellular, biomineralization, and chemical properties of PEEK.