The importance of hypoxia in the progression of cardiovascular diseases like ischemic myocardial infarction, pulmonary hypertension or atherosclerosis among others is well known, while the molecular mechanisms behind the role of HIFs (Hypoxia Inducible Factors) in these pathologies remain largely unexplored. Our main goal is to explore the mechanisms connecting HIF signaling and cardiac disease, with special interest in the developmental origin of heart failure. To this aim, we have generated novel genetic mouse models to understand the implication of VHL/HIF axis in different heart compartments (myocardium, vasculature, epicardium). Using our mouse models, we have reported the fundamental role of VHL/HIF1 signaling in the establishment of metabolic territories in the embryonic heart that are essential for myocardium maturation, ventricular chamber formation and conduction system function (Menendez-Montes et al. 2016). Our results also point to new roles of VHL and HIF2 in the proper formation of cardiac valves (unpublished observations). In addition, we have determined the importance of VHL/HIF2 in coronary development and instability and established a new connection between hypoxia signaling and human coronary diseases (Escobar et al, In preparation). Finally, we are currently exploring the role of hypoxia during cardiac regeneration in the setting of myocardial infarction in neonatal and adult mice. Therefore, our research could contribute to increase our limited knowledge on hypoxia and the cardiovascular system and may have some therapeutic implication.
Ivan Menendez-Montes; Beatriz Escobar Rodriguez; Beatriz Palacios Argandoña; Manuel Jose Gómez Rodriguez; Jose Luis Izquierdo García; Lorena Flores; Luis Jesus Jimenez Borreguero; Julian Aragones Lopez; Jesus Ruiz-Cabello; Miguel Torres Sanchez; Silvia Martin-Puig. Myocardial VHL-HIF signaling controls an embryonic metabolic switch essential for cardiac maturation. Developmental Cell. 39 - 6, pp. 724 - 739. Elsevier, 19/12/2016.
Silvia Martin-Puig; Daniel Tello; Julian Aragones Lopez. Novel perspectives on the PHD-HIF oxygen sensing pathway in cardioprotection mediated by IPC and RIPC. Frontiers in Physiology. 6 - 137, 20/05/2015.
Silvia Martin-Puig; Valentin Fuster; Miguel Torres Sanchez. Heart repair: from natural mechanisms of cardiomyocyte production to the design of new cardiac therapies. Annals of the New York Academy of Sciences. 1254, pp. 71 - 81. 04/2012.
Lei Bu; Xin Jiang; Silvia Martin-Puig; Leslie Caron; S Zhu; Ying Shao; Drucilla J. Roberts; Paul L. Huang; Ibrahim J. Domian; Kenneth R. Chien. Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature. 460 - 7251, pp. 113 - 117. 02/07/2009.
Silvia Martin-Puig; Yibing Qyang; Murali Chiravuri; Susanna Chen; Huansen Xu; Lei Bu; Xin Jiang; L. Lin; Anne Granger; Alessandra Moretti; Leslie Caron; Huansen Xu; John Clarke; MM Taketo; Karl L. Laugwitz; Rhandall T. Moon; Peter Gruber; Sylvia M. Evans; Shen Ding; Kenneth R. Chien. The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway. Cell Stem Cell. 2 - 1, pp. 165 – 179.16/08/2007.