DNA damage and repair on hematopoietic stem cells: impact of oxidative stress in renovascular hypertension

Abstract

ABSTRACT Background This study investigated oxidative damage to bone marrow cells in the pathogenesis of renovascular hypertension (RH). Methods Male C57BL/6 J mice (10-week-old and ~23 g) were divided into two groups: Sham-operated and 2K1C, which has a stainless-steel clip placed around the left renal artery. After twenty-eight days, the animals were anesthetized for hemodynamic measurements and bone marrow cells isolation. The intracellular production of ROS, DNA damage, and DNA repair kinetics were evaluated. Results Our results show that RH increases HSCs ROS production and that the 2K1C group showed a significant reduction of HSCs in the G0/G1 phase, increased p53 expression, DNA fragmentation, low DNA repair capacity, and a higher percentage of apoptotic cells when compared with the Sham group. Conclusions Our data imply that RH can compromise the hematopoiesis by increased oxidative stress leading to impaired DNA repair activity. Furthermore, this study provides new insights into the influence of hypertension on bone marrow homeostasis. This study showed for the first time that RH leads to oxidative damage, including genotoxic, to bone marrow cells. Thus, these findings provide new insights into the consequences of RH on bone marrow cells.