Hypertension (HTN) is one of the most high-impact risk factors for dementia, as high blood pressure imposes a continuous challenge on the brain. Whilst several anti-hypertensive reagents are available, we still lack specific therapies counteracting the detrimental effects of HTN in target organs, such as the brain. Extensive evidence shows that immune cells participate in HTN by infiltrating organ vasculature, and the brain is not an exception. Combining our expertise in cardiovascular physiology, neuroscience and immunology, we aim to dissect the molecular mechanisms regulating the interactions of immune cells with cerebral arteries in HTN, as a step towards identifying novel therapies. Our strategy is to identify the specific T cell subset modifying the structure and function of cerebral arteries in mice challenged with chronic hypertensive stimuli, utilizing a completely novel approach that combine immunophenotyping and sorting of specific T cell population(s) and vascular biology.
Hypertension is one of the major risk factors for stroke, heart failure, cerebrovascular and kidney diseases. Although several therapeutic strategies have been developed against the main components involved in blood pressure regulation (i.e. vasculature; kidney; autonomic nervous system; brain), the prevalence of uncontrolled hypertension continues to rise. The Mosaic Theory of Hypertension highlighted that many factors, including genetics, environment, neural, mechanical, and hormonal perturbations interplay to raise blood pressure. A substantial portion of dysfunctions that accompanies hypertension is mediated by inflammation and immune reaction within target organs. Although there have been extensive studies investigating the T cells involved in hypertension, the mechanism of their contribution to the onset and progression of the disease is still unknown.
Our project investigates the immune-vascular interface in hypertension, with a specific focus in the brain, to obtain a detailed immunophenotyping of T cell subpopulations infiltrating the cerebral vasculature in AngII and DOCA-salt mouse models of hypertension. Furthermore, the candidate T cell subpopulations will be specifically tested for their direct effects on cerebral arteries with the vessel, by an innovative approach through the organ co-culture system. In fact, these activated immune cells in hypertension can affect cognitive function, causing detrimental effects in specific brain areas. Identified functionally-relevant cell types are potential targets for future therapies aimed at complementing the current but insufficient anti-hypertensive drugs. The establishment of a cell therapy could be useful for reducing the progression of hypertension-related cognitive dysfunction. Even if immunotherapies may never be commonly used hypertension treatments, such novel strategies could be essential in patients with aggressive end-organ damage and related cerebrovascular disease. Thus, unravelling novel possibilities of treatment requires a multidisciplinary approach that, considering the many systems contributing to blood pressure regulation, look at them for the crosstalk that regulates their reciprocal interactions.
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