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.                                                 Today's feature paper is going to cause us to rethink the way we prognosticate patients with pulmonary arterial hypertension following their initial management. Think you know the hemodynamic variables? Well, stay tuned for this discussion coming right up after these summaries:                                                 Our first original paper this week shows for the first time the predictive value of coronary artery calcification progression for coronary and cardiovascular events in a population base study. Authors Dr. Erbel and Lehmann from University Hospital Essen in Germany and their colleagues evaluated several progression algorithms between CTs performed at baseline and after a mean of five years for the risk prediction of coronary and cardiovascular events in a population base cohort of more than 3,200 participants initially free from cardiovascular disease.                                                 The authors found that coronary artery calcification progression added some predictive value to the baseline CT and risk assessment, and even when the five-year risk factors were taken into account. However, the progression yielded no additional benefit when the five-year coronary artery calcification results were taken into account instead of the baseline coronary artery calcification results.                                                 Double zero coronary artery calcification scans in a five-year interval meant an excellent prognosis, which was better than the prognosis for incident coronary artery calcification after five years. Thus, the authors concluded that sophisticated coronary artery calcification progression algorithms may be unnecessary and clinicians can instead rely on the most recent risk and coronary artery calcification assessment.                                                 The next paper demonstrates for the first time cell-specific effects of Smad3 signaling in the infarcted myocardium. Now, in the infarcted heart, Smad3 signaling is known to be activated in both cardiomyocytes and the interstitial cells. In the current paper, co-first authors, Doctors Kong and Shinde, corresponding author Dr. Frangogiannis from Albert Einstein College of Medicine in New York, and their colleagues hypothesized that cell-specific actions of Smad3 may regulate, repair, and remodeling in the infarcted myocardium.                                                 In order to dissect the cell-specific Smad3 actions in myocardial infarction, these authors generated mice with Smad3 loss specifically in activated fibroblasts or in cardiomyocytes. They found that fibroblast-specific Smad3 activation played a critical role in repair following myocardial infarction by restraining fibroblast proliferation and contributing to scar organization by stimulating integrin synthesis.                                                 On the other hand, cardiomyocyte-specific Smad3 signaling did not affect acute ischemic injury, but triggered nitrosative stress and induced matrix metalloproteinase expression in the remodeling myocardium, thereby promoting cardiomyocyte death and contributing to systolic dysfunction.                                                 In summary therefore, these authors demonstrated the cellular specificity of Smad3-dependent actions that stimulate distinct cellular responses in fibroblasts versus cardiomyocytes in the healing myocardial infarction. The implications are that nonspecific therapeutic targeting of Smad3 signaling in pathologic conditions may interfere with both detrimental and beneficial actions. On the other hand, design of interventions with specific cellular targets may be