Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g. higher waist-to-hip ratio and fasting insulin levels, but lower body fat). In human adipocyte models, knockdown of FAM13A in preadipocytes accelerates adipocyte differentiation. In mice, Fam13a knockout (KO) have a lower visceral to subcutaneous fat (VAT/SAT) ratio after high-fat diet challenge, in comparison to their wild-type counterparts. Subcutaneous adipocytes in KO mice show a size distribution shift toward an increased number of smaller adipocytes, along with an improved adipogenic potential. Our results indicate that GWAS-associated variants within the FAM13A locus alter adipose FAM13A expression, which in turn, regulates adipocyte differentiation and contribute to changes in body fat distribution.

Background: Clinical importance of hyponatremia in ST-elevation acute myocardial infarction (STEMI) in the era of primary intervention has not been fully understood. The aim of this study was to investigate the impact of hyponatremia on outcomes in patients with STEMI and secondarily to investigate the contribution of arginine vasopressin (AVP) to hyponatremia in STEMI. Methods and Results: Hyponatremia was defined as a sodium concentration <136mmol/L at 72h after hospitalization. First, the short-term (in-hospital mortality or congestive heart failure (CHF)) and long-term prognosis (cardiac death, re-admission for CHF) in STEMI patients was conducted. Second, the relationship between serum sodium level and plasma AVP was investigated. In hyponatremic patients the incidence of in-hospital heart failure was significantly greater (P=0.0018), long-term cardiac death was a higher trend (17.2% vs. 6.3%, P=0.19) and re-admission due to CHF was significantly more frequent (20.7% vs. 4.5%, P=0.0024). Plasma AVP level was higher in the hyponatremia group (4.5 vs. 2.7pg/ml, P=0.003), and it had a negative correlation with serum sodium level (r=-0.28, P=0.02). Conclusions: Hyponatremia was frequently found in the early phase of STEMI, and associated with heart failure in both short- and long-term outcomes. Non-osmotic secretion of AVP could be involved in hyponatremia in STEMI patients. (Circ J 2011; 75: 1927-1933)

Objective: Mechanisms of cardiac dysfunction in myocarditis have not been fully elucidated. Though it remains controversial whether angiogenesis is beneficial or harmful in inflammatory disease, significant vascular destruction might possibly impair cardiac function in myocarditis. The prolyl hydroxylase domain-containing protein (PHD) inhibitor is a potential drug for promoting angiogenesis as it stabilizes hypoxia inducible transcription factor (HIF). The authors examine whether the PHD inhibitor TM6008 could affect cardiac function by promoting angiogenesis in experimental autoimmune myocarditis (EAM). Methods: EAM was induced on BALB/c mice by immunizing them with a synthesized α myosin heavy-chain peptide. Every day, 200 mg/kg of TM6008 or vehicle was administered orally. Results: TM6008 improved left ventricular ejection fraction significantly on the 21st day of EAM. Though TM6008 did not affect the severity of myocardial cell infiltration, it tended to reduce cardiac fibrosis. Immunohistochemistry showed that CD31-positive blood vessels were preserved in the TM6008 group compared to the control group. Immunoblotting revealed that TM6008 increased the expression of HIF-1α, HIF-2α and vascular endothelial growth factor in myocarditis. Conclusion: Inhibition of PHD could ameliorate cardiac dysfunction in EAM, partially through promoting neovascularization. Relief of tissue hypoxia via neovascularization could improve cardiac function in myocarditis.

Extracellular vesicles (EVs) are essential tools for conveying biological information and modulating functions of recipient cells. Implantation of isolated or modulated EVs can be innovative therapeutics for various diseases. Furthermore, EVs could be a biocompatible drug delivery vehicle to carry both endogenous and exogenous biologics. Tracking EVs should play essential roles in understanding the functions of EVs and advancing EV therapeutics. EVs have the characteristic structures consisting of the lipid bilayer and specific membrane proteins, through which they can be labeled efficiently. EVs can be labeled either directly using probes or indirectly by transfection of reporter genes. Optical imaging (fluorescent imaging and bioluminescent imaging), single-photon emission computed tomography (SPECT)/positron emission tomography (PET), and magnetic resonance imaging (MRI) are currently used for imaging EVs. Labeling EVs with superparamagnetic iron oxide (SPIO) nanoparticles for MRI tracking is a promising method that can be translated into clinic. SPIO can be internalized by most of the cell types and then released as SPIO containing EVs, which can be visualized on T2*-weighted imaging. However, this method has limitations in real-time imaging because of the life cycle of SPIO after EV degradation. Further studies will be needed to validate SPIO labeling by other imaging modalities in preclinical studies. The emerging technologies of labeling and imaging EVs with SPIO in comparison with other imaging modalities are reviewed in this paper.