Brief description of the proposal
The increase in life expectancy is generating a rapid growth in the elderly population worldwide and a concomitant increment in the incidence of age-related diseases is expected. Among the elderly populations, neurodegenerative and cardiovascular diseases affect millions of people around the world; this appears as a critical situation that requires an urgent search for innovative preventive and therapeutic approaches. Neurodegenerative and cardiovascular diseases are pathologies characterized by common signatures such as vascular dysfunction and chronic inflammation, which are accelerated with aging. It is already known from experimental and clinical studies that atherosclerosis is associated with a reduced number and dysfunction of endothelial progenitor cells (EPC), crucial players in the maintenance of human vascular homeostasis and endothelial repair at areas of vascular damage.
The endothelium is an essential regulator of vascular homeostasis and dynamic changes in endothelial phenotype can both potentiate and limit atherogenesis and associated complications. Similarly, the blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is crucial in maintaining the homeostasis of the brain microenvironment.
Natural bioactive compounds have been extensively studied for their beneficial effects on a variety of neurodegenerative and cardiovascular diseases. An interesting field of investigation consists in verifying the ability to modulate the classical targets and new emerging biomarkers of endothelium dysfunction and also their potential in protecting from BBB impairment or disruption. ENDO-CARE intends to identify a pool of bioactive compounds that working in mono-treatment or in combination can protect at the same time against both atherosclerosis and BBB dysfunctions acting on specific targets of the endothelium dysfunction.
Advanced and “intelligent” systems of drug delivery (e.g. polymer/lipid based supramolecular assemblies) will be designed to obtain innovative nanocarriers that incorporate a selection of bioactive compounds. In vitro model of BBB and vascular endothelium including mature endothelial cell (EC) and endothelial progenitor cell (EPC) derived from human pluripotent stem cells (hPSCs), will be employed to assess the healthy and protective effect of the bioactive nanocarriers.
The goal of this strategy is to increase the bioavailability of selected bioactive compounds and enhance the biological effects exerted on specific targets by magnifying their synergistic properties when administered at non-pharmacological concentrations, resulting in a double protecting effect against the common earliest events of two different pathological conditions, atherosclerotic cardiovascular disease and dysfunctional BBB-driven CNS disorders.
