title: From endothelial dysfunction to atherosclerosis.
abstract: It has recently emerged that endothelial dysfunction is an early step in the development of atherosclerosis and is mainly characterised by a reduction in the bioavailability of nitric oxide. All of the traditional cardiovascular (CV) risk factors (dyslipidemia, arterial hypertension, hyperglycemia and diabetes) are associated with endothelial dysfunction, and oxidised low-density lipoproteins, the renin-angiotensin axis and insulin resistance play important roles in the pathogenesis of impaired endothelial function. The increased expression of adhesion molecules and pro-inflammatory cytokines leads to abnormal endothelium-dependent vasodilation which could be investigated using vasoreactivity tests such as flow-mediated dilation in the brachial artery. Recently, new evidences showed that the immune system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis with a particular regard towards autoimmunity. The high prevalence of the atherosclerotic process in systemic autoimmune diseases supports the hypothesis of the immune pathogenesis. Evaluating coronary microvascular dysfunction by means of transthoracic echocardiography with non-invasive coronary flow reserve assessment is particularly interesting as it could detect preclinical impairment of coronary microvascular function. The discovery that the mechanisms responsible for endothelial damage have a genetic basis could improve the approach to CV diseases. This review summarises the most important aspects of the pathogenesis and development of endothelial dysfunction, with particular attention to the role of traditional CV risk factors, the usefulness of vasoreactivity tests, and the future perspectives opened by genetic studies.
authors.affiliation: IRCCS Galeazzi Orthopedic Institute, Department of Health Technologies, Università di Milano, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sitia
authors.forename: L
authors.initials: L
authors.lastname: Tomasoni
authors.forename: F
authors.initials: F
authors.lastname: Atzeni
authors.forename: G
authors.initials: G
authors.lastname: Ambrosio
authors.forename: C
authors.initials: C
authors.lastname: Cordiano
authors.forename: A
authors.initials: A
authors.lastname: Catapano
authors.forename: S
authors.initials: S
authors.lastname: Tramontana
authors.forename: F
authors.initials: F
authors.lastname: Perticone
authors.forename: P
authors.initials: P
authors.lastname: Naccarato
authors.forename: P
authors.initials: P
authors.lastname: Camici
authors.forename: E
authors.initials: E
authors.lastname: Picano
authors.forename: L
authors.initials: L
authors.lastname: Cortigiani
authors.forename: M
authors.initials: M
authors.lastname: Bevilacqua
authors.forename: L
authors.initials: L
authors.lastname: Milazzo
authors.forename: D
authors.initials: D
authors.lastname: Cusi
authors.forename: C
authors.initials: C
authors.lastname: Barlassina
authors.forename: P
authors.initials: P
authors.lastname: Sarzi-Puttini
authors.forename: M
authors.initials: M
authors.lastname: Turiel
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015551:Autoimmunity; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics; D017078:Laser-Doppler Flowmetry; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000276:immunology*; D012306:Risk; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D000099291:Adducins