Abstract 562: Plgf is Crucial for the Hypertensive Response and T Cells Infiltration in Target Organs Induced by Angii

Although several therapeutic strategies have been developed against the main components involved in blood pressure (BP) regulation, an optimum control in some hypertensive patients is still flawed, suggesting that mechanisms so far unidentified, sustain BP increase. Interestingly, an emerging area of investigation revealed that adaptive immunity is central in hypertension, since mice devoid of lymphocytes are protected from hypertension, and adoptive transfer of T cells, but not B cells, restores the typical hypertensive response. How hypertensive stimuli can afford this, still represents a fascinating enigma, challenging the search for molecular players, capable to bridge vascular responses to immunity and probably orchestrating the still unveiled role of immune system in hypertension. Among the manifold cytokines and inflammatory mediators, Placental Growth Factor (PlGF), belonging to a family of VEGF related angiogenic factors, caught our attention, given its role of “angiogenic cytokine” and its expression by cells of both the cardiovascular and the immune system. Moreover, it has also been recently shown that PlGF is secreted in vascular cells in response to AngII. Thus, we hypothesized that PlGF might recruit a selected type of immune cell, expressing its receptor VEGFR1, influencing the process of T cells activation during hypertensive challenges. We found that the typical hypertensive response induced by chronic AngII infusion, was completely prevented in mice with genetic deletion of PlGF, as well as the typical end organ damage induced by hypertension, i.e. cardiac hypertrophy, renal damage, microvascular rarefaction and immune cells infiltration in target organs. To determine whether the involvement of PlGF in immune system activation and T cells infiltration during AngII-induced hypertension had a causal role or was merely a consequence of the failure in BP raise, we analyzed both vessels and kidneys, early after AngII infusion, i.e. before BP increase. Strikingly, PlGF absence protected from early infiltration of both CD4+ and CD8+ T cells. Overall our data indicate that PlGF is a pivotal player in the molecular mechanisms activating immune system recruitment during an hypertensive challenge, a central moment in the increase in BP.