Circulating progenitor cells in hypertensive subjects: a treatment with olmesartan and atorvastatin is effective in improving cell number and profile besides expected pharmacological effects

Circulating progenitor cells (CPCs), identified by the expression of surface CD34 antigen, are a population of cells in different states of maturation with the ability to differentiate into different cell types, including cardiomyocytes, smooth muscle cells (SMCs), endothelial progenitor cells (EPCs) and endothelial cells (ECs). CPCs then may participate in the turnover of healthy and damaged tissues of cardiovascular system, delaying the development of atherosclerosis and cardiovascular disease (CVD) and representing a regenerative/reparative potential for CV system. Oxidative stress, and the consequent increased production/accumulation of reactive oxygen species (ROS), is a common feature of CV risk factors including hypertension. ROS, indeed, have a dual role: in high concentrations they are toxic for cells, whereas low ROS levels can participate in intracellular signaling, stimulating mechanisms that prevent tissue injury and promote angiogenesis MicroRNAs (miRs) 221 and 222 have been identified in circulating progenitor cells (CPCs), where they participate in the cell differentiation and proliferation, inhibiting cell migration and homing, also by inhibiting the synthesis of the receptor for the Stem Cell Factor c-Kit. Moreover, miR221/222 modulate different genes regulating the angiogenesis and inflammation. In an “in vitro” study the lowering of miRs in ECs reduced the ROS production and angiogenesis, suggesting a role of miRs in regulating the redox signaling. Previously we found that in CPCs from hypertensive patients without additional risk for CAD, miR221/222 are increased and associated with cell number and production of reactive oxygen species (ROS). The aim of the present study was to evaluate whether in hypertensives a treatment with olmesartan may have effects on the number of CPCs and on levels of miR221/222 and ROS. We also evaluated whether additional effects may be obtained with an add-on treatment with atorvastatin. We included 41 hypertensives (27 M/14 F; mean age 38.1±5.1 years) with no additional risk factor for CAD and 22 matched controls; we evaluated circulating CD34+cell number, intracellular miR221/222 and ROS levels at baseline (T0) and after a six months treatment with 20 mg/die of olmesartan (T1); blood pressure, fibrinogen, CRP, glucose and lipid profile were also evaluated. Then, hypertensives were randomized to receive an add-on treatment with atorvastatin (T2a), or to continue with olmesartan alone (T2p) for further 3 months. All parameters were evaluated at the end of the study period. At T1, systolic and diastolic blood pressure (Δ: -13.5 and -19.5, respectively, both p<0.001), ROS (Δ: -17.5, p<0.001) and miR221/222 (Δ: -13% and -21%, respectively, p=0.002 and p<0.001, respectively) were significantly decreased with respect to T0, while the number of cells was increased (Δ: +22.4%, p<0.001). CRP and fibrinogen levels were also reduced (Δ: -25.4% and -11.5%, respectively, p<0.001 and p=0.005, respectively). After the treatment with atorvastatin (T2a) ROS, miRs, CRP and fibrinogen levels were further decreased (Δ: -23.6%; -31.1%; -46.3%; -26.8%, and -14.1%; p <0.005 for ROS, miRs, CRP; p<0.01 for fibrinogen), and CPCs significantly higher (Δ: +25.0%, p=0.004); blood pressure values also were further reduced, while lipid profile amelioration didn’t reached the statistical significance. At T2p no further changes were detected as compared to T1. Olmesartan is effective in reducing miRs and ROS levels in CPCs from hypertensives, as well as in increasing CPC number. An add-on treatment with atorvastatin may improve these effects.