title: The angiogenic factor PlGF mediates a neuroimmune interaction in the spleen to allow the onset of hypertension.
abstract: Hypertension is a health problem affecting over 1 billion people worldwide. How the immune system gets activated under hypertensive stimuli to contribute to blood pressure elevation is a fascinating enigma. Here we showed a splenic role for placental growth factor (PlGF), which accounts for the onset of hypertension, through immune system modulation. PlGF repressed the expression of the protein Timp3 (tissue inhibitor of metalloproteinases 3), through the transcriptional Sirt1-p53 axis. Timp3 repression allowed costimulation of T cells and their deployment toward classical organs involved in hypertension. We showed that the spleen is an essential organ for the development of hypertension through a noradrenergic drive mediated by the celiac ganglion efferent. Overall, we demonstrate that PlGF mediates the neuroimmune interaction in the spleen, organizing a unique and nonredundant response that allows the onset of hypertension.
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy; Department of Molecular Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Carnevale
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pallante
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Fardella
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Fardella
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Iacobucci
authors.affiliation: Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cifelli
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: De Lucia
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, Neuro and Cardiovascular Pathophysiology Research Unit, IRCCS Neuromed, 86077 Pozzilli, Italy; Department of Molecular Medicine, "Sapienza" University of Rome, 00161 Rome, Italy. Electronic address: lembo@neuromed.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lembo
mesh_terms: D000804:Angiotensin II / Q000276:immunology; D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000276:immunology*; D005728:Ganglia, Sympathetic; D006973:Hypertension / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015213:Neuroimmunomodulation; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; D019717:Tissue Inhibitor of Metalloproteinase-3; D016159:Tumor Suppressor Protein p53; D000804:Angiotensin II; D000072483:Placenta Growth Factor; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1