Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.                                                 Current guidelines recommend measurement of one of the cardiac specific isoforms of cardiac troponin complex. However, what's the utility of combining measurements of troponins I and T in the early diagnosis of acute myocardial infarction? Well, you have to wait for our upcoming feature discussion, but it's coming right up after these summaries.                                                 The first original paper this week sheds light on the genetic basis and mechanisms of bicuspid aortic valve, the most common congenital heart defect in the population. We know that bicuspid aortic valve is an autosomal dominant trait with variable expression and incomplete penetrants suggestive of genetic and environmental modifiers. In the current study, first author Dr Gharibeh, corresponding author Dr Nemer from University of Ottawa, and authors of the Bicuspid Aortic Valve Consortium assessed cardiac structure and function in mice, lacking a GATA6 allele. They found that GATA6 heterozygous mice had a highly penetrant type of bicuspid aortic valve with right and left leaflet fusion, which is the most frequent type found in humans. GATA6 transcript levels were lower in human bicuspid aortic valve as compared to normal tricuspid valves. Mechanistically, GATA6 haploinsufficiency disrupted valve remodeling and extracellular matrix composition through dysregulation of the importance in the molecules including matrix metalloproteinase nine. Cell-specific inactivation of GATA6 reveal that an essential rule for GATA6 in secondary heart field myocytes. Thus, the study identifies a new cellular and molecular mechanism underlying bicuspid aortic valve.                                                 In the field of cardiac regeneration, c-Kit positive adult progenitor cells were initially reported to produce new cardiomyocytes in the heart. However, more recent genetic evidence suggests that such events are exceedingly rare. Today's paper provides insights into this discrepancy and it is from first author Dr Maliken, corresponding author, Dr Molkentin from Howard Hughes Medical Institute Cincinnati Children's Hospital Medical Center. The authors took a novel approach of deleting the necessary cardiogenic transcription factors, GATA4 and GATA6, from c-Kit expressing cardiac progenitor cells to determine whether true de novo cardiomyocyte formation would occur. They found that deletion of the necessary cardiogenic transcription factors, GATA4 and GATA6, from these c-Kit+ cardiac progenitor cells remarkably resulted in greater apparent cardiomyocyte derivation from the c-Kit+ cells. Deletion of GATA4 from c-Kit–derived endothelial progenitors altered the integrity of the endothelial cell network in the heart, resulting in greater c-Kit+–derived leukocytes entering the heart and fusing with cardiomyocytes.                                                 Thus, they demonstrated a new role for GATA4 in endothelial differentiation, specifically showing for the first time that GATA4 is essential for vascular development by the c-Kit lineage. The study shows that leukocyte to cardiomyocyte fusion is the primary basis for path lineage tracing results, incorrectly suggesting that c-Kit+ cardiac progenitor cells generated de novo cardiomyocytes in the heart.                                                 Lecithin–cholesterol acyltransferase, or LCAT, is the sole enzyme that esterifies cholesterol in the plasma. Its role in the supposed protection from atherogenesis remains unclear, because mutations in LCAT can cause more or less carotid atherosclerosis. Addressing this conundrum, co-first authors Drs. Oldoni and Baldassarre, co-corresponding authors Dr