AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR.

Background: The sarcoplasmic reticulum (SR) Ca-ATPase 2 (SERCA2) mediates Ca reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca release from SR and triggers contraction. Ca/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca signals remain elusive.

Glycosylated Chromogranin A in Heart Failure: Implications for Processing and Cardiomyocyte Calcium Homeostasis.

Background: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function.

Methods And Results: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands.

Secretoneurin is a novel prognostic cardiovascular biomarker associated with cardiomyocyte calcium handling.

Background: Secretoneurin (SN) levels are increased in patients with heart failure (HF), but whether SN provides prognostic information and influences cardiomyocyte function is unknown.

Objectives: This study sought to evaluate the merit of SN as a cardiovascular biomarker and assess effects of SN on cardiomyocyte Ca(2+) handling.

Methods: We assessed the association between circulating SN levels and mortality in 2 patient cohorts and the functional properties of SN in experimental models.

Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway.

Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload.

Time-course of experimental choroidal neovascularization in Dutch-Belted rabbit: clinical and histological evaluation.

In order to study the pathogenesis of choroidal neovascularization (CNV) and explore a suitable animal model for assessing anti-angiogenic agents, rabbit CNV was induced by subretinal injection of a cocktail containing endotoxin and growth-factor, incorporated in Heparin-sepharose beads. The presence and development of CNV lesions was visualized by fluorescein angiography and quantified by image analysis. The time-course of experimental CNV was evaluated clinically and histologically, with some lesions followed up to 3-years.