BackgroundEven though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted.MethodsWe conducted a cross-sectional study of 562 elderly Japanese men aged 60–69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension.ResultsIn the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12)).Conclusionsγ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.
Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60-69 years who participated in a general health checkup at least twice from 2014-2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. this study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects. Recently, bone marrow-derived hematopoietic stem cells (immature cells, such as CD34+ cells) have been revealed to play a major role in vascular homeostasis 1-3. It is likely that the number of circulating CD34+ cells could indicate the capacity of endothelial maintenance 4-6. However, it is known that hematopoietic bone marrow activity declines with age 7-10 , which might induce a lower capacity of endothelial maintenance in elderly subjects. Furthermore, aging is a well-known cause of endothelial injury 11,12 which subsequently induces endothelial repair. In addition, the aggressive endothelial repair that causes atherosclerosis might induce a wasting reduction of circulating CD34+ cells 6,13 which result in a shortage of the mediators of endothelial repair. Moreover, inadequate endothelial repair might cause hypertension in elderly individuals 14. These previous studies indicate that there are close connections among the age-related decline of bone marrow activity, age-related endothelial injury, and the wasting reduction of circulating CD34+ cells. Platelets are also known to play an important role in vascular inflammation and vessel wall remodeling 15,16. Indeed, platelets promote the mobilization of bone marrow-derived CD34+ cells into the peripheral blood 17-21 , and CD34+ cells also induce platelet elevation 22,23. Furthermore, platelets have been reported to play an important role in the initial development of atherosclerotic lesions 24 , and not only induce the differentiation of human CD34+ cells into endothelial cells, but also into foam cells, which contribute to the development of atherosclerosis 25. Therefore, platelets also play an important role in the a...
Aim: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells.Methods: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/μL) as the cut-off.Results: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [β] = −0.22, P = 0.014), but not for participants with high levels (β = −0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (β = −0.02, P = 0.865), significant positive associations were identified for participants with high levels (β = 0.22, P = 0.028). Conclusions:As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis.
Recent studies have revealed an inverse association between height and cardiovascular disease and that endothelial progenitor cells (CD34-positive cells) contribute to vascular maintenance, which is associated with cardiovascular disease. However, evidence of the association between height and CD34-positive positive cells among elderly participants is limited. To assess this association, we conducted a cross-sectional study of 231 elderly Japanese men aged 65–69. Since enhanced production of circulating CD34-positive cells in response to endothelial injury might act have a strong confounding effect on the association between height and circulating CD34-positive cells, the median value for the levels of these cells (0.93 cells/μL) was used to stratify the participants. Multivariable linear regression analysis demonstrated that height was significantly positively associated with circulating CD34-positive cells for those participants with low levels of circulating CD34-positive cells (n=114) but not for those with higher levels (n=117), with a multi-adjusted standardized parameter estimate (β) of 0.27 (p=0.008) for low and 0.11 (0.275) for higher circulating CD34-positive cell levels. The positive association is limited to participants with relatively low circulating CD34-positive cell levels, whose productivity of these cells is not activated. Our findings indicate that height is an indicator of vascular maintenance capability in elderly Japanese men.
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