Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis.

Congenital heart defects often result from improper differentiation of cardiac progenitor cells. Although transcription factors involved in cardiac progenitor cell differentiation have been described, the associated chromatin modifiers in this process remain largely unknown. Here we show that mouse embryos lacking the chromatin-modifying enzyme histone deacetylase 3 (Hdac3) in cardiac progenitor cells exhibit precocious cardiomyocyte differentiation, severe cardiac developmental defects, upregulation of Tbx5 target genes and embryonic lethality. Hdac3 physically interacts with Tbx5 and modulates its acetylation to repress Tbx5-dependent activation of cardiomyocyte lineage-specific genes. These findings reveal that Hdac3 plays a critical role in cardiac progenitor cells to regulate early cardiogenesis.

Impact of Wire Sensor Location on Coronary Physiological Measurement.

BACKGROUND: The location of the wire sensor to measure fractional flow reserve (FFR) and diastolic pressure ratio (dPR) has not been systematically studied. Therefore, we hypothesize that the coronary physiological measurements will vary with the location of the sensor. METHODS: Fifty-four patients were screened, and 30 consecutive patients were enrolled. The OptoWire 2 or 3 generation fiberoptic pressure wire was used to assess whole cycle pressure distal/pressure aorta, dPR, and FFR. Our primary goal is to test if those measurements vary with the wire sensor placed at 10 mm (proximal), 35-45 mm (mid), and greater than or equal to 60-70 mm (distal) distal to the target lesion, respectively. We used a multilevel linear regression approach. RESULTS: Of 30 patients enrolled, 23 (76.6%) were males, mean age was 64.7 years (± 11.0 years), and mean stenosis was 61.6% (±13.4%). Adjusting for age, gender, and severity of stenosis, results showed that for all 3 measures (whole cycle pressure distal/pressure aorta, dPR, and FFR), pressure decreased in a linear fashion the further the sensor was from the target lesion ( P < 0.001). Further, pairwise comparisons of the measurements at adjacent locations similarly showed significant declines in pressure ( P < 0.001). CONCLUSIONS: This is the first study to demonstrate that the location of the pressure wire can impact the results of both resting and hyperemic pressures, which can cause a false-negative result. This is especially important where the values are near the cutoff.