Ricerc@Sapienza

Each year 3 to 4 million women and men with signs/symptoms suggestive of myocardial ischemia have no obstructive ischemic heart disease (IHD). Although the same number of women and men die annually from cardiovascular disease, women are more likely to have no obstructive IHD compared to men. The mechanisms underlying this pathological state are not known and treatment guidelines are missing. Our hypothesis is that in patients with no obstructive IHD, platelets are hyperactive and promote a pro-inflammatory state in which dysfunctional recruitment and activation of leukocytes lead to coronary microvascular dysfunction and ultimately to no obstructive IHD. The objective of the study is to understand how platelet and immune dysfunctions determine no obstructive IHD and whether sex differences in platelet reactivity and immunity explain why women are more likely to have this form of ischemia compared to men. To achieve this objective we propose three tasks to be pursued by a coordinated effort of three research units. The Unit of V. Raparelli will be in charge of patient evaluation and recruitment and sample collection (task 1). The samples will be collected from adults included in the Endocrine Vascular disease Approach (EVA) project (ClinicalTrials.gov identifier NCT02737982), an observational cohort prospective study currently in recruiting phase. The Unit of L. Stefanini will employ time-resolved flow cytometry to investigate whether platelets circulate in a pre-activated and pro-inflammatory state in patients with no obstructive IHD (task 2). The Unit of S. Piconese will perform immunological profiling of patients with multiparameter flow cytometry-based techniques (task 3). In summary, the proposed project will employ state-of-the-art flow cytometry techniques to dissect the mechanisms underlying no obstructive IHD, an emerging clinical issue especially for women. We anticipate that these studies will facilitate the tailoring of safer sex-specific therapies.