|Department||Department of Biochemistry and Molecular Biology|
|Institution||University of Texas Southwestern Medical Center at Dallas|
|Address||6000 Harry Hines Blvd. 75235|
|City, State, Zip||Dallas, TX 75390|
|Research Field||Cardiovascular Disease/Cellular Biology|
|Country of Origin||Peru|
|Mentor||Dr. Joseph A. Hill|
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. In response to hypertension and stress, the heart develops a strong pathological hypertrophic growth, which offsets cardiac wall stress pointing towards heart failure. We and others have demonstrated that the activation of autophagy, a highly conserved lysosomal-mediated process of protein and organelle recycling, is required for the manifestation of hypertrophy. Nevertheless, the mechanism by which autophagy is activated during hypertrophy is not understood. The primary cilium is a protuberant membrane structure located at the surface of the cell membrane, which, in response to changes in the fluid flow or pressure can “bend” activating intracellular pathways, depending on cell type, tissue and stimuli. We propose that the “primary cilium” is a key player in the mechanotransduction of signals in the heart during pressure overload stress. The mechanosensory function of primary cilia in renal, nodal, and endothelial cells, as well as in embryonic heart, is mediated principally by polycystin-1 (PKD1) and polycystin-2 (PKD2) which are the products of the PKD genes. Reports have shown that mutations and dysfunction in PKD2 can trigger polycystic kidney disease, cardiovascular abnormalities, hypertension, intracranial aneurysms and left-right asymmetry aberrations. Evidence regarding the presence and function of the cilia in the heart is poor. Furthermore, the role of cilia and its functional protein PKD2 in the regulation of pathological hypertrophy and autophagy is completely unknown. Our work will determine how the cilia sense the overload stress in the heart and will investigate how autophagy can be regulated by cilia during hypertrophy. Our aim is that this work will provide promising new avenues for the prevention and treatment of heart disease.
- Boechi, Leonardo
- Carreño, Leandro J.
- Criollo, Alfredo C.
- Fuxman Bass, Juan I.
- Giudice, Jimena
- Kahn, Suzana A.
- Martin, Natalia
- Pereira, Renata M.
- Pérez-Cuesta, Luis María
- Silva Manzano, Daniel Adriano