Increased LDL electronegativity in chronic kidney disease disrupts calcium homeostasis resulting in cardiac dysfunction.

Chronic kidney disease (CKD), an independent risk factor for cardiovascular disease, is associated with abnormal lipoprotein metabolism. We examined whether electronegative low-density lipoprotein (LDL) is mechanistically linked to cardiac dysfunction in patients with early CKD. We compared echocardiographic parameters between patients with stage 2 CKD (n = 88) and normal controls (n = 89) and found that impaired relaxation was more common in CKD patients. Reduction in estimated glomerular filtration rate was an independent predictor of left ventricular relaxation dysfunction. We then examined cardiac function in a rat model of early CKD induced by unilateral nephrectomy (UNx) by analyzing pressure-volume loop data. The time constant of isovolumic pressure decay was longer and the maximal velocity of pressure fall was slower in UNx rats than in controls. When we investigated the mechanisms underlying relaxation dysfunction, we found that LDL from CKD patients and UNx rats was more electronegative than LDL from their respective controls and that LDL from UNx rats induced intracellular calcium overload in H9c2 cardiomyocytes in vitro. Furthermore, chronic administration of electronegative LDL, which signals through lectin-like oxidized LDL receptor-1 (LOX-1), induced relaxation dysfunction in wild-type but not LOX-1(-/-) mice. In in vitro and in vivo experiments, impaired cardiac relaxation was associated with increased calcium transient resulting from nitric oxide (NO)-dependent nitrosylation of SERCA2a due to increases in inducible NO synthase expression and endothelial NO synthase uncoupling. In conclusion, LDL becomes more electronegative in early CKD. This change disrupts SERCA2a-regulated calcium homeostasis, which may be the mechanism underlying cardiorenal syndrome.

Optical behavior and structural property of CuAlS2 and AgAlS2 wide-bandgap chalcopyrites.

Single crystals of CuAlS2 and AgAlS2 were grown by chemical vapor transport method using ICl3 as the transport. The as-grown CuAlS2 crystals reveal transparent and light-green color. Most of them possess a well-defined (112) surface. The AgAlS2 crystals essentially show transparent and white color in vacuum. As the AgAlS2 was put into the atmosphere, the crystal surface gradually darkened and became brownish because of the surface reaction with humidity or hydrogen gas. After a long-term chemical reaction process, the AgAlS2 will transform into a AgAlO2 oxide with yellow color. From x-ray diffraction measurements, both CuAlS2 and AgAlS2 as-grown crystals show single-phase and isostructural to a chalcopyrite structure. The (112) face is more preferable for the formation of the chalcopyrite crystals. The energies of interband transitions of the CuAlS2 and AgAlS2 were determined accurately by thermoreflectance measurements in a wide energy range of 2-6 eV. The valence-band electronic structures of CuAlS2 and AgAlS2 have been detailed and characterized using polarized-thermoreflectance measurements in the temperature range between 30 and 300 K. The band-edge transitions belonging to the E(∥) and E(⊥) polarizations have been, respectively, identified. The band edge of AgAlS2 is near 3.2 eV while that of AgAlS2 is about 3.5 eV. On the basis of the experimental analyses, optical and sensing behaviors of the chalcopyrite crystals have been realized.