Cardiovascular System

We are investigating the function of FGF receptor signaling in specific cardiovascular lineages. We have shown that endothelial FGF receptor signaling is essential for wound healing, and the hearts response to ischemia-reperfusion injury. FGF receptors are being targeted in cardiomyocytes and stromal cells of the heart and other tissues to address their role in tissue homeostasis, and ischemia-reperfusion injury.

Cardiovascular publications:

  1. Woo KV, Ornitz DM, Singh GK. Diagnosis and Pathophysiological Mechanisms of Group 3 Hypoxia-Induced Pulmonary Hypertension. Current treatment options in cardiovascular medicine. 2019;21(3):16 PubMed: PMID30903302.
  2. Oladipupo SS, Kabir AU, Smith C, Choi K, Ornitz DM. Impaired tumor growth and angiogenesis in mice heterozygous for Vegfr2 (Flk1). Sci Rep. 2018;8(1):14724 PubMed: PMID30283071.
  3. Park C, Lee TJ, Bhang SH, Liu F, Nakamura R, Oladipupo SS, Pitha-Rowe I, Capoccia B, Choi HS, Kim TM, Urao N, Ushio-Fukai M, Lee D, Miyoshi H, Kim BS, Lim DS, Apte RS, Ornitz DM, Choi K. Injury-Mediated Vascular Regeneration Requires Endothelial ER71/ETV2. Arterioscler Thromb Vasc Biol. 2016;36(1):86-96 PMCID: PMC4690812.
  4. House SL, Castro AM, Lupu TS, Weinheimer C, Smith C, Kovacs A, Ornitz DM. Endothelial fibroblast growth factor receptor signaling is required for vascular remodeling following cardiac ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2016;310(5):H559-71 PMCID: PMC4796602.
  5. House SL, Wang J, Castro AM, Weinheimer C, Kovacs A, Ornitz DM. Fibroblast growth factor 2 is an essential cardioprotective factor in a closed-chest model of cardiac ischemia-reperfusion injury. Physiological reports. 2015;3(1):e12278-e PMCID: PMC4387743.
  6. Oladipupo SS, Smith C, Santeford A, Park C, Sene A, Wiley LA, Osei-Owusu P, Hsu J, Zapata N, Liu F, Nakamura R, Lavine KJ, Blumer KJ, Choi K, Apte RS, Ornitz DM. Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis. Proc Natl Acad Sci U S A. 2014;111(37):13379-84 PMCID: PMC4169958.
  7. Lavine KJ, Epelman S, Uchida K, Weber KJ, Nichols CG, Schilling JD, Ornitz DM, Randolph GJ, Mann DL. Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc Natl Acad Sci U S A. 2014;111(45):16029-34 PMCID: 4234568.
  8. Kim JY, Lee RH, Kim TM, Kim DW, Jeon YJ, Huh SH, Oh SY, Kyba M, Kataoka H, Choi K, Ornitz DM, Chae JI, Park C. OVOL2 is a critical regulator of ER71/ETV2 in generating FLK1+, hematopoietic, and endothelial cells from embryonic stem cells. Blood. 2014;124(19):2948-52 PMCID: PMC4224193.
  9. Cilvik SN, Wang JI, Lavine KJ, Uchida K, Castro A, Gierasch CM, Weinheimer CJ, House SL, Kovacs A, Nichols CG, Ornitz DM. Fibroblast growth factor receptor 1 signaling in adult cardiomyocytes increases contractility and results in a hypertrophic cardiomyopathy. PLoS One. 2013;8(12):e82979 PMCID: PMC3859602.
  10. Vega-Hernández M, Kovacs A, De Langhe S, Ornitz DM. FGF10/FGFR2b signaling is essential for cardiac fibroblast development and growth of the myocardium. Development. 2011;138(15):3331-40 PMCID: PMC3133922.
  11. Lavine KJ, Ornitz DM. The Epicardial Signaling Center in Development and Disease. In: Rosenthal N, Harvey R, editors. Heart Development and Regeneration. First ed. London: Elsevier Inc.; 2010. p. 345-59.
  12. Lavine KJ, Ornitz DM. Shared Circuitry: Developmental signaling cascades regulate both embryonic and adult coronary vasculature. Circ Res. 2009;30(104(2)):159-69 PMCID: PMCID: PMC2757940.
  13. Lavine KJ, Schmid G, Smith CS, Ornitz DM. Novel tool to suppress cell proliferation in vivo demonstrates that myocardial and coronary vascular growth represent distinct developmental programs. Dev Dyn. 2008;237(3):713-24 PMCID: PMID: 18297725.
  14. Lavine KJ, Ornitz DM. Fibroblast Growth Factors and Hedgehogs: At the Heart of the Epicardial Signaling Center. Trends Genet. 2008;24(1):33-40 PMCID: PMID: 18054407.
  15. Lavine KJ, Long F, Choi K, Smith C, Ornitz DM. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Development. 2008;135(18):3161-71 PMCID: PMID: 18725519.
  16. Lavine KJ, Kovacs A, Ornitz DM. Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice. J Clin Invest. 2008;118(7):2404-14 PMCID: PMC2430494.
  17. White AC, Lavine KJ, Ornitz DM. FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network. Development. 2007;134(20):3743-52 PMCID: PMC2099314.
  18. Lavine KJ, Ornitz DM. Rebuilding the coronary vasculature: hedgehog as a new candidate for pharmacological revascularization. Trends Cardiovasc Med. 2007;17(3):77-83.
  19. Hung IH, Yu K, Lavine KJ, Ornitz DM. FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod. Dev Biol. 2007;307(2):300-13 PMCID: PMC2267922.
  20. Park C, Lavine K, Mishina Y, Deng CX, Ornitz DM, Choi K. Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation. Development. 2006;133(17):3473-84 PubMed: PMID16887829.
  21. Lavine KJ, White AC, Park C, Smith CS, Choi K, Long F, Hui CC, Ornitz DM. Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes Dev. 2006;20(12):1651-66 PMCID: PMCID: PMC1482484.
  22. Lavine KJ, Yu K, White AC, Zhang X, Smith C, Partanen J, Ornitz DM. Endocardial and epicardial derived FGF signals regulate myocardial proliferation and differentiation in vivo. Dev Cell. 2005;8(1):85-95 PubMed: PMID15621532.