Circulating progenitor cells in hypertensive subjects: Effectiveness of a treatment with olmesartan in improving cell number and miR profile in addition to expected pharmacological effects

Abstract

CD34+ circulating progenitor cells (CD34+CPCs) are a population of multipotent cells which can delay the development of atherosclerosis and cardiovascular disease (CVD) in conditions of increased CV risk. MicroRNAs (miRs) 221 and 222 modulate different genes regulating angiogenesis and inflammation; moreover, miR221/22 have beenshown to participate in differentiation and proliferation of CD34+CPCs, inhibiting cell migration and homing. miR221/222 in CD34+CPCs from hypertensive subjects are also increased and associated with CD34+cell number and reactive oxygen species (ROS). We evaluated CD34+CPC number, intracellular miR221/222 and ROS levels, arterial stiffness (AS)and echocardiography indices at baseline (T0).Then, after a six-month treatment with olmesartan, 20 mg/day (T1), in 57 hypertensive patients with left ventricular hypertrophy (LVH) and with no additional risk factor for CVD, and in 29 healthy controls (baseline),fibrinogen, C-reactive protein (CRP), glucose and lipid profiles were also evaluated.At T1, blood pressure values, CRP and fibrinogen levels, ROS and miR221/222 were significantly decreased (all p <0.001), as were AS indices and LV mass index (p<0.001), while cell number was increased (p<0.001). Olmesartan is effective in reducing miR and ROS levels in CD34+CPCs from hypertensive subjects, as well as in increasing CD34+CPC number, providing multilevel CV protection, in addition to its expected pharmacological effects.

Circulating levels of CD34+ cells predict long-term cardiovascular outcomes in patients on maintenance hemodialysis

“…Therefore, low CD34 + cell counts are considered a characteristic of patients on maintenance HD therapy and maybe a meaningful predictive factor. Some drugs such as angiotensin II receptor antagonist, statin and erythropoietin have been shown to affect the number of circulating CD34 + cell[24,25]. However, there was no favorable effect of these drugs on the levels of CD34 + cells in our cohort, probably because chronic HD patients had low capacity to produce CD34 + cells.…”

Effects of Angiotensin-Converting Enzyme Inhibition on Circulating Endothelial Progenitor Cells in Patients with Acute Ischemic Stroke

“…Indeed, Mandraffino et al [ 60 ] showed a strong correlation between inflammatory markers (including CRP and fibrinogen) and EPC levels in several different clinical settings (smokers, arthritis patients, and hypertensive patients with and without left ventricular hypertrophy); here, it was stated that “CD34+ cell count change at T1 appeared to be mainly correlated with fibrinogen reduction (Rs = −0.625, p < 0.001).” This group also proposed different mechanisms through which inflammation (including mediators, cytokines, receptors, and microRNAs), and also RAAS modulation (including drug intervention) might affect the EPC number [ 53 – 58 ]. Moreover, the relationships between fibrinogen and EPCs have also been evaluated in elderly individuals, where inflammatory markers appear to lose their predictive ability [ 59 ]. Our study showed that serum fibrinogen and hsCRP levels were significantly higher in group Ia, although multiple linear regression did not reveal them to be independent factors affecting EPC mobilization.…”

Role of miR-221/222 in Tumor Development and the Underlying Mechanism

“…It is important that the miR-221/222 expression level is closely related to tumor stage and prognosis. It may be used as a biomarker for the diagnosis of premalignant tumors [104] and provide a new target for tumor therapy [8-33, 35, 38, 51, 94], as a therapeutic tool for drug resistance or sensitivity to anticancer drugs [127].…”