Abstract:
Objective To explore the association of the levels of angiogenic T(T
ang) cells and immunologic senescence, pro-inflammatory capacity of these cells with endothelial dysfunction and systemic inflammation in hypertensive patients. Methods A total of 120 untreated inpatients with essential hypertension from the Department of Hypertension and Vascular Disease in the First Affiliated Hospital of Sun Yat-sen University were enrolled from September 2019 to March 2020. Flow-mediated dilation(FMD) of brachial artery was used to evaluate endothelial function. Based on FMD≤7% and >7%, patients were divided into two groups according to the presence and absence of vascular endothelial dysfunction. Proportion of CD28
null andCD28
+ in CD4
+/CD8
+subset of T
ang cellsCD3
+CD31
+CXC chemokine receptor-4(CXCR4)
+ in peripheral blood and γ-interferon(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), interleukin-10(IL-10) positive cells, and the expression of CD57, CD27(serve as senescent profiles), CC-chemokine receptor 7(CCR7)and human telomerase reverse transcriptase(hTERT) were measured by flow cytometry. Levels of serum cytokines including IL-6,interleukin-17(IL-17), IFN-γ,TNF-α were detected by enzyme-linked immunosorbent assay(ELISA). The baseline data, biochemical indicators, T
ang cells subsets, and serum inflammatory differences of two groups were compared. Pearson correlation analysis were used to analyze the correlation between the subset of CD28
null CD4
+T
ang cells and FMD, serum cytokines. Logistic regression and receiver operating characteristic(ROC) curve were used to determine the association and diagnostic efficacy of T
ang cell subsets for endothelial dysfunction. Results The proportion of CD28
null subset was significantly higher in CD4
+ T
ang cells in hypertensive patients with endothelial dysfunction, which was negatively correlated with FMD(r=-0.643, P<0.01). Multiple logistic regression analysis showed that higher proportion of CD28
nullCD4
+T
ang cells was associated with endothelial dysfunction(OR=3.428, 95%CI 1.423-5.012, P<0.001), with good diagnostic performance in endothelial dysfunction area under curve(AUC)=0.885, P<0.001. Immunophenotyping revealed that CD57 expression was increased, and CCR7, CD27, hTERT expression were decreased in CD28
nullCD4
+T
ang cells, indicating senescence. The proportion of IL-6, IFN-γ and TNF-α positive cells were higher. CD28
nullCD4
+T
ang cell number was significantly associated with the serum levels of IL-6, IL-17, IFN-γ and TNF-α in hypertensive patients. Conclusion Subset of T
ang cells with senescent and proinflammatory phenotype, associated with FMD and systemic inflammation, may serve as a biological marker for assessing endothelial dysfunction in hypertensive patients.