Rationale: Endothelial progenitor cells (EPCs) are present in the systemic circulation and home to sites of ischemic injury where they promote neoangiogenesis. β 2 -Adrenergic receptor (β 2 AR) plays a critical role in vascular tone regulation and neoangiogenesis. Objective: We aimed to evaluate the role of β 2 AR on EPCs’ function. Methods and Results: We firstly performed in vitro analysis showing the expression of β 2 AR on EPCs. Stimulation of wild-type EPCs with β-agonist isoproterenol induced a significant increase of Flk-1 expression on EPCs as assessed by fluorescence-activated cell sorter. Moreover, β 2 AR stimulation induced a significant increase of cell proliferation, improved the EPCs migratory activity, and enhanced the EPCs’ ability to promote endothelial cell network formation in vitro. Then, we performed in vivo studies in animals model of hindlimb ischemia. Consistent with our in vitro results, in vivo EPCs’ treatment resulted in an improvement of impaired angiogenic phenotype in β 2 AR KO mice after induction of ischemia, whereas no significant amelioration was observed when β 2 AR knock out (KO) EPCs were injected. Indeed, wild-type–derived EPCs’ injection resulted in a significantly higher blood flow restoration in ischemic hindlimb and higher capillaries density at histological analysis as compared with not treated or β 2 AR KO EPC-treated mice. Conclusions: The present study provides the first evidence that EPCs express a functional β 2 AR. Moreover, β 2 AR stimulation results in EPCs proliferation, migration, and differentiation, enhancing their angiogenic ability, both in vitro and in vivo, leading to an improved response to ischemic injury in animal models of hindlimb ischemia.

Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD.

Endothelial dysfunction (ED) is a systemic disorder characterized by reduced production of nitric oxide. This pathologic condition, which impairs vascular homeostasis, leads to the loss of protective properties of endothelial cells and is related to the pathogenesis of cardiovascular diseases. ED may affect every vascular bed, accounting for several clinical implications, particularly when the coronary bed is affected. Although the reliability of ED as a cardiovascular disease surrogate is still debated, many methods for its assessment have been proposed. In this review, we underline the clinical value of ED in the cardiovascular field and summarize the principal methods currently available for its assessment.

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Objective: Obesity is an independent cardiovascular risk factor, but its prognostic role in patients with peripheral arterial disease (PAD) is not well defined. Accordingly, we assessed the impact of body mass index (BMI) and waist circumference (WC) on cardiovascular risk in a homogeneous cohort of PAD patients. Methods: BMI and WC were measured in 190 consecutive PAD patients with ABI o0.90, referred to our university hospital for intermittent claudication. The occurrence of cardiac, cerebrovascular and peripheral events was prospectively assessed. The ability to classify risk was determined by calculating the hazard ratios (HRs) and c-statistics. Results: During a median follow-up of 31.5 months, 63 patients (33.2%) had a cardiovascular event. Considered as continuous variables, both adiposity indices were significantly associated with increased cardiovascular risk, even after adjustment for possible confounding factors (HR ¼ 1.08, 95% CI 1.01-1.15, P ¼ 0.045 for BMI and HR ¼ 1.04, 95% CI 1.01-1.07, P ¼ 0.004 for WC). When BMI and WC were included together in a fully adjusted Cox model, the significant association between BMI and cardiovascular risk disappeared (HR ¼ 0.98, 95% CI 0.88-1.10, P ¼ 0.772), whereas WC remained significantly associated with a worse outcome (HR ¼ 1.04, 95% CI 1.01-1.08, P ¼ 0.033). The better discriminative ability of WC vs BMI was confirmed by the c-statistic, which was significantly higher for WC (0.63, 95% CI 0.56-0.70) than for BMI (0.56, 95% CI 0.51-0.63, P ¼ 0.038). Conclusions: Abdominal obesity and, to a lesser degree, general obesity worsen the prognosis of PAD patients independently of possible confounding factors. Weight reduction should be integrated in the active management of these patients.