Signal transduction in cardiovascular biology
- Chieh-Yu Lin.
- Dec. 2013.
- Physical description
- online resource (ix, 192 pages) : illustrations (some color)
- Includes bibliographical references (p. 179-192). 144 refs.
- The cardiovascular system provides blood circulation throughout the body and is essential for our survival. The major components of the circuitry--the heart, the valves, and the vasculature--require precise signaling events for their prenatal morphogenesis and postnatal homeostasis. Here, we describe the role of cell signaling in cardiovascular biology. In the arterial system, VEGF/Vegfr-2 signaling is essential for vascular remodeling. A pulse of VEGF/Vegfr-2 signaling in the vascular adventitia within hours after vascular injury activates Sca1+ tissue stem cells to differentiate into adventitial and neointimal cells, forming the neointima that occludes the vessel. In the myocardium, calcineurin/NFAT signaling controls cardiac fiber orientation and the expression of dystrophin, a-dystrobrevin, and utrophin--components of the dystrophin glycoprotein complex frequently found abnormal in patients with Duchenne, Becker, or other muscular dystrophies. Deletion of calcineurin in the myocardium results in cardiomyopathy, a phenotype similar to that observed in Duchenne muscular dystrophy patients. In the secondary heart field, calcineurin/NFATc1 signaling is required for semilunar valve morphogenesis. Conditional ablation of calcineurin or NFATc1 causes regression of heart valve primordium, leading to complete absence of the aortic and pulmonic valves, severe valve regurgitation, and perinatal lethality. These studies demonstrate novel functions and molecular mechanisms of cell signaling in three facets of cardiovascular biology.
- Calcineurin > metabolism
- Heart Valves > embryology
- Signal Transduction
- Vascular Remodeling > physiology
- Embryonic Stem Cells > metabolism
- Myocardium > metabolism
- NFATC Transcription Factors
- Vascular Endothelial Growth Factor A > metabolism
- Publication date
- Submitted to the Program in Cancer Biology and the Committee on Graduate Studies of Stanford University.
- Thesis (Ph.D.)--Stanford University, 2013.