Rationale: Major coronary vessels derive from the proepicardium, the cellular progenitor of the epicardium, coronary endothelium, and coronary smooth muscle cells (CoSMCs Key Words: retinoic acid Ⅲ heart development Ⅲ coronary Ⅲ smooth muscle Ⅲ endothelium C oronary morphogenesis has been receiving intense scrutiny because of its usefulness as a model to understand vascular development and as a source of cues for regenerative therapies. Coronary vessel morphogenesis is linked to the development of epicardium and proepicardium, a transient embryonic structure located between the sinus venosus and the liver primordium. 1,2 Avian embryos have been instrumental to our knowledge on coronary development. Lineagetracing studies indicate that the proepicardium contains precursors of the epicardium, coronary endothelial cells (CoEs) and coronary smooth muscle cells (CoSMCs). [2][3][4][5] Proepicardial and primitive epicardial cells undergo epithelial-to-mesenchymal transformation (EMT), 2,6 supplying mesenchymal cells to the outer surface of the heart. These epicardially derived cells occupy positions along the subepicardial space, where they will differentiate into coronary vessel cell types. 7 Around Hamburger-Hamilton stage (HH)26, highly migratory, epicardially derived cells leave the subepicardium to invade the myocardium, thus disseminating part of CoE progenitors throughout the cardiac muscle. 8,9 Coronary vessels are formed from primary subepicardial and intramyocardial endothelial plexuses. Subepicardial/intramyocardial coronary vessel morphogenesis display one of the most striking and least understood features of coronary development, ie, the pronounced delay between CoE/CoSMC differentiation. Already at stage HH24, precursors in subepicardium differentiate into CoEs and form endothelial tubes under the influence of myocardially secreted cytokines, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. 10,11 In contrast, full CoSMC differentiation is only apparent after HH31 to HH32, concomitant with connection of CoE network to the aorta, stabilization of directional blood flow, and the onset of shear stress on coronary endothelium. 11 Curiously, CoSMC differentiation is Original

Carriers of TXNIP genetic variants presented higher TXNIP expression, early signs of glucose homeostasis derangement and increased susceptibility to chronic metabolic conditions such as diabetes and hypertension. Our data suggest that genetic variation in the TXNIP gene may act as a "common ground" modulator of both traits: diabetes and hypertension.

We and others have provided evidence that adipose tissue-derived mesenchymal stem cells (ASCs) can mitigate rat cardiac functional deterioration after myocardial ischemia, even though the mechanism of action or the relevance of these findings to human conditions remains elusive. In this regard, the porcine model is a key translational step, because it displays heart anatomic-physiological features that are similar to those found in the human heart. Towards this end, we wanted to establish the cultural characteristics of porcine ASCs (pASCs) with or without long-term cryostorage, considering that allogeneic transplantation may also be a future option. Compared to fresh pASCs, thawed cells displayed 90–95% viability and no changes in morphological characteristics or in the expression of surface markers (being pASCs characterized by positive markers CD29+; CD90+; CD44+; CD140b+; CD105+; and negative markers CD31−; CD34−; CD45− and SLA-DR−; n = 3). Mean population doubling time was also comparable (64.26±15.11 hours to thawed cells vs. 62.74±18.07 hours to fresh cells) and cumulative population doubling increased constantly until Passage 10 (P10) in the entire cell population, with a small and gradual increase in senescence (P5, 3.25%±0.26 vs. 3.47%±0.32 and P10, 9.6%±0.29 vs. 10.67%±1.25, thawed vs. fresh; SA-β-Gal staining). Chromosomal aberrations were not observed. In addition, under both conditions pASCs responded to adipogenic and osteogenic chemical cues in vitro. In conclusion, we have demonstrated the growth characteristics, senescence, and the capacity of pASCs to respond to chemical cues in vitro and have provided evidence that these properties are not influenced by cryostorage in 10% DMSO solution.

The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker associated with Type 2 diabetes mellitus (T2DM) risk. Nonetheless, its functional role in disease pathology is poorly understood. The aim of the present study was to investigate, in vascular smooth muscle cells from 92 patients undergoing aortocoronary bypass surgery, the contribution of this SNP in T2DM using expression levels and expression correlation comparison approaches, which were visually represented as gene interaction networks. Initially, the expression levels of 41 genes (seven TCF7L2 splice forms and 40 other T2DM relevant genes) were compared between rs7903146 wild-type (CC) and T2DM-risk (CT + TT) genotype groups. Next, we compared the expression correlation patterns of these 41 genes between groups to observe if the relationships between genes were different. Five TCF7L2 splice forms and nine genes showed significant expression differences between groups. RXRα gene was pinpointed as showing the most different expression correlation pattern with other genes. Therefore, T2DM risk alleles appear to be influencing TCF7L2 splice form's expression in vascular smooth muscle cells, and RXRα gene is pointed out as a treatment target candidate for risk reduction in individuals with high risk of developing T2DM, especially individuals harboring TCF7L2 risk genotypes.

No abstract