Mandraffino G, Imbalzano E, Sardo M A, D'Ascola A, Mamone F, Lo Gullo A, Alibrandi A, Loddo S, Mormina E, David A, Saitta A
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy.
J Hum Hypertens. 2014 Sep;28(9):543-50. doi: 10.1038/jhh.2014.7. Epub 2014 Feb 20.
We investigated whether different degrees of hypertension-related cardiovascular involvement are associated with changes in circulating proangiogenic hematopoietic cell (PHC) numbers and/or phenotypes and/or in the PHC redox system in hypertensive individuals with isolated arterial stiffening (AS) hypertensives or with both carotid intima-media thickening and left ventricular hypertrophy (LVH) hypertensives. We also evaluated microRNA (miRs) 221 and 222 (miRs221/222) expression in CD34+ cells, the relationship between these miRs and cell number and reactive oxygen species (ROS) levels, and the expression of manganese superoxide dismutase (MnSOD), catalase (CAT) glutathione peroxidase type-1 (GPx-1) and gp91phox-containing nicotinamide-adenine-dinucleotide-phosphate-oxidase (NOX2). Proangiogenic hematopoietic cells (PHCs) from hypertensive patients and controls were isolated by flow cytometry. PHCs were higher in hypertensives than in controls but were lower in LVH than in AS hypertensives. In CD34+ cells from AS hypertensives, NOX2, MnSOD, CAT and GPx-1 were overexpressed; ROS, miRs and NOX2 were also increased and were associated with cell number. In LVH, we found an imbalance in the cell redox system; MnSOD showed the highest values, whereas CAT and GPx-1 were lower than in AS hypertensives. Intracellular ROS, miRs and NOX2 were higher and inversely associated with cell number. In AS hypertensives, the redox balance may sustain the increase in PHCs; by contrast, in hypertensives with more advanced lesions, redox imbalance may result in increased oxidative stress and cell reduction.
我们研究了不同程度的高血压相关心血管受累是否与单纯动脉僵硬度增加(AS)的高血压患者或同时伴有颈动脉内膜中层增厚和左心室肥厚(LVH)的高血压患者循环中促血管生成造血细胞(PHC)数量、表型及/或PHC氧化还原系统的变化相关。我们还评估了CD34+细胞中微小RNA(miR)221和222(miR221/222)的表达、这些miR与细胞数量和活性氧(ROS)水平之间的关系,以及锰超氧化物歧化酶(MnSOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶1型(GPx-1)和含gp91phox的烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX2)的表达。通过流式细胞术分离高血压患者和对照者的促血管生成造血细胞(PHC)。高血压患者的PHC高于对照者,但LVH患者的PHC低于AS高血压患者。在AS高血压患者的CD34+细胞中,NOX2、MnSOD、CAT和GPx-1过表达;ROS、miR和NOX2也增加,且与细胞数量相关。在LVH患者中,我们发现细胞氧化还原系统失衡;MnSOD值最高,而CAT和GPx-1低于AS高血压患者。细胞内ROS、miR和NOX2更高,且与细胞数量呈负相关。在AS高血压患者中,氧化还原平衡可能维持PHC的增加;相比之下,在病变更严重的高血压患者中,氧化还原失衡可能导致氧化应激增加和细胞减少。