Cellules endothéliales circulantes, microparticules et progéniteurs : vers la définition de la « vasculocompétence »

Exposure to deleterious processes of metabolic, infectious, autoimmune or mechanical origin, alters the endothelium which progresses towards a proinflammatory and procoagulant activation, senescence and apoptosis. This “response to injury” of the endothelium plays a key role in the initiation and progression of cardiovascular disorders. In the last 10 years, identification in peripheral blood of circulating endothelial cells (CEC) and endothelial-derived microparticles (EMP) reflecting endothelium damage has led to the development of new noninvasive methods for endothelium exploration. Indeed, these biomarkers were associated with most of the cardiovascular risk factors, were correlated with established parameters of endothelial dysfunction, and were indicative of a poor clinical outcome. Moreover, they behave as biological vectors able to disseminate deleterious signals in the vascular compartment. More recently, this concept has been enlarged by the discovery of a potent repair mechanism based on the recruitment of the circulating endothelial progenitors cells (EPC) from the bone marrow, able to regenerate injured endothelial cells. Cardiovascular risk factors alter EPC number and function. Because the damage/repair balance plays a critical role in the endothelium homeostasis, CEC, EMP and EPC could be combined in an endothelium phenotype that defines the “vascular competence” of each individual. In the future, progress in standardization of available methodologies to measure these emerging biomarkers is a crucial step to establish their clinical interest for assessment of vascular risk and monitoring of vascular-directed therapeutics.     

Increasing procoagulant activity of circulating microparticles in patients living with HIV

ObjectivesHIV-infected individuals are at higher risk of non-AIDS diseases associated with procoagulant status. Microparticles are elevated in disorders associated with thrombosis (e.g., cardiovascular diseases). We investigated the association between microparticle levels in untreated and treated HIV-infected subjects, and determined the association with immune status, viral replication, and duration of antiretroviral therapy.Patients and methodsWe included 144 HIV-infected subjects, including 123 on antiretroviral therapy (ART) and 21 before treatment initiation. A control group of 40 HIV-negative healthy adults matched for age and sex was used for comparison of microparticle levels. Treated subjects were divided into five groups depending on the period of antiretroviral exposure. Statistically significant differences were determined by Kruskal–Wallis test and Chi² test. The relation between microparticles and other parameters was assessed using Spearman's coefficient of correlation.ResultsMicroparticle levels were significantly higher in treated and untreated HIV-infected subjects than in non-HIV-infected controls (P < 0.001). The microparticle level was similar between the groups on treatment (P = 0.913). No association between the microparticle level and CD4+ count, CD4+/CD8+ ratio, number of HIV-1 RNA copies, or duration of exposure to antiretroviral treatment was observed.ConclusionIncreased levels of microparticles may be due to processes independent of viral replication and CD4+ cell count, and microparticle release might persist even during viral suppression by antiretroviral treatment. Elevated microparticle levels might occur in response to other triggers.     

Value of left atrial dilation in the diagnosis of silent myocardial ischemia in diabetes mellitus patients

BACKGROUND: Accelerated atherothrombosis is a common feature in diabetes mellitus patients (DM), which can be related to abnormalities in vascular cell apoptosis and activation leading to the release of procoagulant microparticles (MPs). In DM patients, we hypothesized that circulating levels of biomarkers involved in atherothrombosis processes as well as cardiac and carotid echocardiography variables could be useful in the detection of silent myocardial diagnosed by myocardial perfusion imaging. METHODS AND RESULTS: We investigated, in 55 patients with diabetes (mean age 62+/-10 years) and 15 nondiabetics (46+/-14 years) patients the prevalence of silent myocardial ischemia (SMI) detected by a treadmill exercise or dipyridamole ((99m))Tc-sestamibi stress test. Echocardiographic and -carotid variables were obtained using standardized methods. Biomarkers assessing endothelial apoptosis or activation (CD31(+)-MPs, CD62(+)-MPs, VCAM-1), inflammatory status (CD11a+/-MPs, MCP-1, CRP), platelet activation (GPIb+/-MPs, CD40-L, P-selectin, GPV) ventricular stretch (BNP) were measured in the plasma. SMI was diagnosed in 23/55 (42%) diabetics patients and in 3/15 (20%) nondiabetics patients. Enhanced inflammatory status and leukocyte damage (CD11a(+)-MPs) were evidenced in diabetic patients. Within the diabetic population, biomarkers levels of atherothrombosis were not significantly associated to the detection of SMI. In multivariable analyses adjusted for LV hypertophy, left atrial surface (LA) remained independent predictor of silent myocardial ischemia (OR 4.14; IC [1.7-16.13]; P=0.039). CONCLUSIONS: In diabetes mellitus patients, LA surface independently predicted silent myocardial ischemia after adjustment for established echocardiographic, and inflammatory risk factors. This simple measure of LA dilation could be helpful in the identification of diabetes mellitus patients at heightened cardiovascular risk.     

Markers of thrombotic disease: procoagulant microparticles

Thrombosis remains one of the leading causes of mortality and morbidity in developed countries. Relevant markers of the primary thrombotic risk however remain of limited accessibility, and clinicians are left with markers of essentially etiological nature. Fortunately, new entities, testifying to cellular activation or damage within the vascular compartment, have been recently described and are in the validation process. Microparticles (MP) are plasma membrane fragments released by stimulated or apoptotic cells. In the vascular compartment, they constitute a disseminated storage pool of bioactive effectors involved in inflammation, thrombosis, vascular tone, angiogenesis. Their biological characteristics are predetermined by the cytosolic and membraneous components hijacked from the activated cells. Their procoagulant properties are based on, (i) the accessibility of phosphatidylserine, a procoagulant aminophospholipid exposed after stimulation and necessary for the assembly of the blood clotting enzyme complexes, and (ii) the possible presence of tissue factor, the major initiator of the coagulation cascade. The incidence of MP in haemostatic processes has been demonstrated in physiology and pathology. They are now considered true pathogenic markers of the thrombotic risk.