Reply: Transforming Growth Factor β1– and Bone Morphogenetic Protein 2/PPARγ–regulated MicroRNAs in Pulmonary Arterial Hypertension

From the Authors:

Dr. Calvier and colleagues highlight valuable new information about additional microRNAs and their role in vascular metabolism in pulmonary hypertension. As evidenced by their elegant work and emphasized in our article (1), the list of microRNAs that are important in various aspects of pulmonary hypertension will undoubtedly continue to expand. In that context, an ongoing challenge in this field will be to discern regulatory hierarchies of how these molecules collaborate and interface with one another to elicit a final pathobiological effect. Strategies to achieve such insights will likely require a combination of more reliable in vivo or ex vivo models of pulmonary hypertension (2), more detailed molecular -omics profiling of those models, and more sophisticated computational approaches to analyze the resulting data (3). In regard to disease modeling, it will become increasingly important to develop models that can provide a platform to define the spatiotemporal relationships of these microRNAs within the vascular compartment, that is, to determine where and when the microRNAs are activated or repressed. To gain this level of insight, it likely will also be necessary to develop and/or standardize methods for quantifying and detecting alterations of microRNA expression and function, perhaps even in real time, from disease inception to end stage. As a scientific community, if we are able to achieve such levels of sophistication in our studies, we will have a much greater opportunity to leverage that information for diagnostic and therapeutic benefit in this otherwise exceedingly complicated pathobiology.