Circulating CD34+ cells and active arterial wall thickening among elderly men: A prospective study

Abstract

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...

Relationships of handgrip strength with the presence of cerebral microbleeds and platelet count in older Japanese adults

“…However, low bone marrow activity may limit the proliferation of platelets, leading to poor endothelial repair. Disruption of the microvascular endothelium impairs the microcirculation [20]. Thus, people with a low platelet count may be at higher risk of microcirculatory dysfunction in the brain, leading to CMBs, and in muscle, leading to lower handgrip strength and the progression of physical frailty (Figure 1).…”

“…Platelets are initiators of vascular inflammation and vessel wall remodeling [18,19], and age-related increases in inflammatory agents can disrupt the microvascular endothelium. In turn, disruption of the microvascular endothelium impairs the microcirculation and prevents delivery of the oxygen and nutrients necessary to maintain skeletal muscle mass [20]. Moreover, failure of the cerebrovascular endothelium is the underlying mechanism of cerebral small vessel disease, including CMBs [21].…”

Possible mechanisms underlying the association between human T-cell leukemia virus type 1 (HTLV-1) and hypertension in elderly Japanese population

“…Since atherosclerosis is the process of aggressive endothelial repair [30], the number of platelets can indicate the level of endothelial repair activity [31]. Therefore, a high level of platelets and the presence of hematopoietic stem cells are mandatory for the development of atherosclerosis [32].…”

Reduced Renal Function and Stroke Subtypes

“…In this way, reduced renal function could be associated with arteriosclerosis (small artery)-related stroke, such as lacunar infarction and intracerebral hemorrhage. Furthermore, because platelet also takes an important role in endothelial repair 6) , thrombosis could be induced in the process of endothelial repair. Therefore, reduced renal function can be associated with all types of stroke.…”

“…However, after adjusting for age, those significant associations disappeared. Because aging is associated with increased risk of endothelial injury and reduced activity of endothelial repair 6) , aging could influence both reduced renal function and hemorrhagic stroke by disrupting microcirculation. In other words, age-related disruption of microcirculation could cause both hemorrhagic stroke and reduced renal function.…”