Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1 + progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1 -cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1 + cells did not. We therefore believe that the SSEA-1 + progenitors that we have described here have the potential to be used in cardiac regenerative medicine.

Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.

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Taken together, data on the mechanical and reactive properties of radial and internal mammary arteries show why the radial artery displayed a higher potential for spasm than the internal mammary artery and why the use of Ca2+ channel blocker can decrease the incidence of occlusion and spasm.

Abstract-Recent studies indicate that cardiac T-type Ca 2ϩ current (I CaT ) reappears in hypertrophied ventricular cells. The aim of this study was to investigate the role of angiotensin II (Ang II), a major inducer of cardiac hypertrophy, in the reexpression of T-type channel in left ventricular hypertrophied myocytes. We induced cardiac hypertrophy in rats by abdominal aorta stenosis for 12 weeks and thereafter animals were treated for 2 weeks with losartan (12 mg/kg per day), an antagonist of type 1 Ang II receptors (AT 1 ). In hypertrophied myocytes, we showed that the reexpressed I CaT is generated by the Ca V 3.1 and Ca V 3.2 subunits. After losartan treatment, I CaT density decreased from 0.40Ϯ0.05 pA/pF (nϭ26) to 0.20Ϯ0.03 pA/pF (nϭ27, PϽ0.01), affecting Ca V 3.1-and Ca V 3.2-related currents. The amount of Ca V 3.1 mRNA increased during hypertrophy and retrieved its nonhypertrophic level after losartan treatment, whereas the amount of Ca V 3.2 mRNA was unaffected by stenosis. In cultured newborn ventricular cells, chronic Ang II application (0.1 mol/L) also increased I CaT density and Ca V 3.1 mRNA amount. UO126, a mitogen-activated protein kinase kinase-1/2 (MEK1/2) inhibitor, reduced Ang II-increased I CaT density and Ca V 3.1 mRNA amount. Bosentan, an endothelin (ET) receptor antagonist, reduced Ang II-increased I CaT density without affecting the amount of Ca V 3.1 mRNA. Finally, cotreatment with bosentan and UO126 abolished the Ang II-increased I CaT density. Our results show that AT 1 -activated MEK pathway and autocrine ET-activated independent MEK pathway upregulate T-type channel expression. Ang II-increased of I CaT density observed in hypertrophied myocytes may play a role in the pathogenesis of Ca 2ϩ overload and arrhythmias seen in cardiac pathology.

This paper shows the interaction of the cardiotonic agent 4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole-2-carbonitrile Membrane Preparations and Cell Cultures. Rat brain synaptosomes and guinea pig brain cortical vesicular preparations were isolated as described (11,12). Primary cultures of rat skeletal myoblasts, chicken and rat cardiac cells, and cells of the NiE 115 neuroblastoma cell line and of the C9 cell line were prepared and grown as described (13) tTo whom reprint requests should be addressed. 896The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Various aspects of early right ventricular remodeling were analyzed in this model. This model reproduced evolving right ventricular alterations secondary to chronic volumetric and barometric overload, as observed in repaired tetralogy of Fallot with usual sequelae, and can be used for therapeutic innovation.

The long-lasting after-hyperpolarization(s) (AHP) that follows the action potential in rat myotubes differentiated in culture is due to Ca2+-activated K+ channels. These channels have the property to be specifically blocked by the bee venom toxin apamin at low concentrations.