Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells.

Human-induced pluripotent stem cells (h-iPSCs) are a unique in vitro model for cardiovascular research. To realize the potential applications of h-iPSCs-derived cardiomyocytes (CMs) for drug testing or regenerative medicine and disease modeling, characterization of the metabolic features is critical. Here, we show the transcriptional profile during stages of cardiomyogenesis of h-iPSCs-derived CMs. CM differentiation was not only characterized by the expression of mature structural components (MLC2v, MYH7) but also accompanied by a significant increase in mature metabolic gene expression and activity. Our data revealed a distinct substrate switch from glucose to fatty acids utilization for ATP production. Basal respiration and respiratory capacity in 9 days h-iPSCs-derived CMs were glycolysis-dependent with a shift towards a more oxidative metabolic phenotype at 14 and 28 day old CMs. Furthermore, mitochondrial analysis characterized the early and mature forms of mitochondria during cardiomyogenesis. These results suggest that changes in cellular metabolic phenotype are accompanied by increased O2 consumption and ATP synthesis to fulfill the metabolic needs of mature CMs activity. To further determine functionality, the physiological response of h-iPSCs-derived CMs to ß-adrenergic stimulation was tested. These data provide a unique in vitro human heart model for the understanding of CM physiology and metabolic function which may provide useful insight into metabolic diseases as well as novel therapeutic options.

Chest pain in hospitalized patients: cause-specific and gender-specific differences.

OBJECTIVES: The aim of this prospective cardiological-linguistic study was to assess cause-specific and gender-specific differences in the reported symptoms and description of chest pain. METHODS: In patients hospitalized because of chest pain, location, radiation, quality of chest pain, pain precipitating and relieving factors, and additional symptoms were assessed. The cause of chest pain was assessed as either coronary or noncoronary. Patients' pain descriptions were taped for linguistic narrative analysis and transcribed according to ethnomethodological standards. RESULTS: The cause of chest pain was assessed as coronary in 43 (18 females, 25 males, mean age 63 years) and noncoronary in 49 (30 females, 19 males, mean age 62 years) patients. Only few cause-related differences in the symptoms were found. In patients with a coronary cause, the location of chest pain was more often retrosternal (93% vs. 71%, p = 0.0078), in the right arm (23% vs. 6%, p = 0.0186), and less often in the back (28% vs. 51%, p = 0.0241) than in patients with a noncoronary cause of chest pain. Coronary patients more often had a pressing pain quality (81% vs. 61%, p = 0.034), less often pain precipitated by respiration (16% vs. 45%, p = 0.0032), and vertigo (21% vs. 43%, p = 0.0252) than noncoronary patients. The women were older than the men (mean age 65.6 vs. 59.0 years, p = 0.01). Women with a coronary cause more often had a gradual pain onset (78% vs. 48%, p = 0.0488) and relief by rest (78% vs. 40%, p = 0.0139) than men with a coronary cause. Linguistic analysis revealed that men presented themselves as interested in the cause of the chest pain, observing and describing pain concretely, whereas women presented themselves as prevailingly pain enduring, describing their pain diffusely. CONCLUSIONS: Cause-related and gender-related differences in symptoms are too unspecific to distinguish between coronary and noncoronary causes. The strong gender differences in self-presentation and description of chest pain might be an explanation for underdiagnosis and undertreatment of women with coronary heart disease and should be considered when taking the clinical history of a female patient.