The Effect of Sex Differences on Endothelial Function and Circulating Endothelial Progenitor Cells in Hypertriglyceridemia

Abstract

Background. Men have a higher risk and earlier onset of cardiovascular diseases compared with premenopausal women. Hypertriglyceridemia is an independent risk factor for the occurrence of ischemic heart disease. Endothelial dysfunction is related to the development of ischemic heart disease. Whether sex differences will affect the circulating endothelial progenitor cells (EPCs) and endothelial function in hypertriglyceridemia patients or not is not clear. Methods. Forty premenopausal women and forty age- and body mass index (BMI)-matched men without cardiovascular and metabolic disease were recruited and then divided into four groups: normotriglyceridemic women (women with serum triglycerides level <150 mg/dl), hypertriglyceridemic women (women with serum triglycerides level ≥150 mg/dl), normotriglyceridemic men (men with serum triglycerides level <150 mg/dl), and hypertriglyceridemic men (men with serum triglycerides level ≥150 mg/dl). Peripheral blood was obtained and evaluated. Flow-mediated dilatation (FMD), the number and activity of circulating EPCs, and the levels of nitric oxide (NO), vascular endothelial growth factor (VEGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma and culture medium were measured. Results. The number and activity of circulating EPCs, as well as the level of NO in plasma or culture medium, were remarkably increased in premenopausal females compared with those in males both in the hypertriglyceridemic group and the normotriglyceridemic group. The EPC counts and activity, as well as the production of NO, were restored in hypertriglyceridemic premenopausal women compared with those in normal women. However, in hypertriglyceridemic men, the EPC counts and activity, as well as levels of NO, were significantly reduced. The values of VEGF and GM-CSF were without statistical change. Conclusions. The present study firstly demonstrated that there were sex differences in the number and activity of circulating EPCs in hyperglyceridemia patients. Hypertriglyceridemic premenopausal women displayed restored endothelial functions, with elevated NO production, probably mediated by estradiol. We provided a new insight to explore the clinical biomarkers and therapeutic strategies for hypertriglyceridemia-related vascular damage.

New Technologies With Increased Precision Improve Understanding of Endothelial Cell Heterogeneity in Cardiovascular Health and Disease

“…Sexual dimorphism in ECs has been observed and provides insight into sex-based differences that may affect the risk of vascular diseases (Stanhewicz et al, 2018). Compared with men, premenopausal women with hypertriglyceridemia were found to have increased levels of progenitor ECs, along with enhanced production of nitric oxide required for vascular homeostasis, indicating a protective role for these ECs against vascular disease in women (Ren et al, 2020). Additionally, female cultured human umbilical ECs showed higher expression of genes involved in cell proliferation and migration than did male human umbilical ECs.…”

Endothelial Progenitor Cell Levels and Extent of Post-prandial Lipemic Response

“…Studies have shown that HDL increases the number and activity of EPCs ( 41 – 43 ). Various studies have shown that circulating EPCs are reduced in the presence of classic CVD risk factors ( 44 ), non-modifiable risk factors such as age and gender also affect the number of EPCs ( 45 ). Accordingly, it has been determined that older people have fewer CD34 + KDR + cells than younger people and men have fewer CD34 + KDR + cells than women.…”

“…Accordingly, it has been determined that older people have fewer CD34 + KDR + cells than younger people and men have fewer CD34 + KDR + cells than women. The number of EPCs may be a factor in explaining the protection of fertile women from CVD risk ( 45 ). It can be claimed that the risk of CVD is higher in people with a low EPC count because these people have impaired endothelial repair and compensatory angiogenesis.…”

“…Accordingly, it has been determined that older people have fewer CD34 + KDR + cells than younger people and men have fewer CD34 + KDR + cells than women. The number of EPCs may be a factor in explaining the protection of fertile women from CVD risk (45).…”

The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair

“…Hypertriglyceridemia has also been shown to negatively affect EPC biology. Hypertriglyceridemia leads to endothelial dysfunction and injury by interfering with SDF-1/CXCR-4 binding and NO pathways, thus affecting mobilization, migration, homing, and the vasculogenic properties of EPC [ 60 , 61 ].…”