Non-productive angiogenesis disassembles A ss plaque-associated blood vessels
Por:
Alvarez-Vergara, M, Rosales-Nieves, A, March-Diaz, R, Rodriguez-Perinan, G, Lara-Urena, N, San Luis, C, Sanchez-Garcia, M, Martin-Bornez, M, Gomez-Galvez, P, Vicente-Munuera, P, Fernandez-Gomez, B, Marchena, M, Bullones-Bolanos, A, Davila, J, Gonzalez-Martinez, R, Trillo-Contreras, J, Sanchez-Hidalgo, A, del Toro, R, Scholl, F, Herrera, E, Trepel, M, Korbelin, J, Escudero, L, Villadiego, J, Echevarria, M, de Castro, F, Gutierrez, A, Rabano, A, Vitorica, J and Pascual, A
Publicada:
25 may 2021
Ahead of Print:
25 may 2021
Resumen:
The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around A ss plaques. Here we demonstrate that angiogenesis is started near A ss plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around A ss plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of A ss pathology. We also show that A ss plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD. A ss are extracellular deposits relevant in Alzheimer's disease (AD). This study shows that A ss plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.
Filiaciones:
Alvarez-Vergara, M:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Rosales-Nieves, A:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
March-Diaz, R:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Rodriguez-Perinan, G:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Lara-Urena, N:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
San Luis, C:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin D2, Ireland
Sanchez-Garcia, M:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Edinburgh, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh, Midlothian, Scotland
Martin-Bornez, M:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Gomez-Galvez, P:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Biol Celular, Seville, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Vicente-Munuera, P:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Biol Celular, Seville, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fernandez-Gomez, B:
CSIC, Inst Cajal, Grp Neurobiol Desarrollo GNDe, Madrid, Spain
Marchena, M:
CSIC, Inst Cajal, Grp Neurobiol Desarrollo GNDe, Madrid, Spain
Univ Europea Madrid, Fac Ciencias Biomed & Salud, Dept Med, Villaviciosa De Odon, Spain
Bullones-Bolanos, A:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Davila, J:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Malaga, Fac Ciencias, Inst Invest Biomed Malaga IBIMA, Dept Biol Celular Genet & Fisiol, Malaga, Spain
:
Univ Miguel Hernandez, Inst Neurociencias Alicante, Consejo Super Invest Cient, CSIC,UMH, Alicante, Spain
Trillo-Contreras, J:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Fisiol Med & Biofis, Seville, Spain
Sanchez-Hidalgo, A:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Fisiol Med & Biofis, Seville, Spain
del Toro, R:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Fisiol Med & Biofis, Seville, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
Scholl, F:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Fisiol Med & Biofis, Seville, Spain
Herrera, E:
Univ Miguel Hernandez, Inst Neurociencias Alicante, Consejo Super Invest Cient, CSIC,UMH, Alicante, Spain
Trepel, M:
Augsburg Med Ctr, Dept Hematol & Oncol, Augsburg, Germany
Korbelin, J:
Univ Med Ctr Hamburg Eppendorf, Dept Oncol Hematol & Stem Cell Transplantat, Sect Pneumol, Hamburg, Germany
Escudero, L:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Univ Seville, Dept Biol Celular, Seville, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Villadiego, J:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Seville, Dept Fisiol Med & Biofis, Seville, Spain
Echevarria, M:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Seville, Dept Fisiol Med & Biofis, Seville, Spain
de Castro, F:
CSIC, Inst Cajal, Grp Neurobiol Desarrollo GNDe, Madrid, Spain
:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Malaga, Fac Ciencias, Inst Invest Biomed Malaga IBIMA, Dept Biol Celular Genet & Fisiol, Malaga, Spain
Rabano, A:
Fdn CIEN, Madrid, Spain
Vitorica, J:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Seville, Fac Farm, Dept Bioquim & Biol Mol, Seville, Spain
Pascual, A:
Univ Seville, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, CSIC, Seville, Spain
Green Published, gold
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