C.O. Aragona

Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease.

Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

Biglycan expression in current cigarette smokers: A possible link between active smoking and atherogenesis

OBJECTIVE Cigarette smokers present early signs of vascular damage and systemic inflammation. Biglycan (BGN), an ubiquitous component of extracellular matrix orchestrating several physiological functions, has recently been indicated as a major source of low-density lipoprotein retention in the normal arterial intima-media layer. We evaluated whether BGN-mRNA expression was enhanced in peripheral monocytes of smokers with no additional cardiovascular risk factors (CVRFs), and if it was associated with altered carotid arterial stiffness (AS) or intima media thickness (cIMT). We also evaluated plasma markers of systemic and vascular inflammation, and correlation with BGN-mRNA. METHODS Two-hundred-fifty-one young smokers were enrolled, with no additional CVRFs, and 60 controls. Plasma lipids, fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), AS and cIMT were assessed. A smoke exposure index (SEIx) was calculated. RESULTS Fibrinogen, CRP, AS indices, cIMT, and BGN-mRNA were higher in smokers compared to controls; HDL-C levels were lower, no difference was detected in IL-6 levels. After stratification of smokers in quartiles based on SEIx values, smokers in the highest quartiles presented highest fibrinogen, CRP, AS, cIMT, BGN, and also IL-6 values, and lowest HDL-C. CONCLUSION BGN-mRNA was enhanced in young smokers, compared to controls, and appears associated to a proatherogenic profile, characterized by increased fibrinogen, CRP, and IL-6, lower HDL-C, altered AS and cIMT values, particularly in those with higher SEIx: the more cigarettes smoked over years, the more marked the alterations. Although we cannot state whether BGN have a direct causal role in inducing, maintaining and developing vascular damage, including intima-media wall thickening and arterial stiffening, our data could suggest that it may represent a link between proatherogenic status induced by cigarette smoking, and the development and progression of vascular damage.

Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia remodelling in refractory Takayasu arteritis

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that involves large and mediumsized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report a 19 years old female patient with TA refractory to conventional immunosuppressive agents, successfully treated with subcutaneous tocilizumab, a humanized monoclonal antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging tool to follow up the patient. Currently, clinical indices of disease activity, inflammatory markers, carotid intima media thickness (cIMT) as well as carotid pulse wave velocity (cPWV) normalised, while the prednisone dosage has been tapered. Tocilizumab appears to be a good option in refractory TA, with a remarkable steroid-sparing effect. In addition, it seems to have a favourable effect on endothelial function, as it improved cIMT and PWV.