High anti-human cytomegalovirus antibody levels are associated with the progression of essential hypertension and target organ damage in Han Chinese population

Abstract

Human cytomegalovirus (CMV) infection is associated with hypertension and has been linked with the pathogenesis of increased arterial blood pressure (BP). Currently, whether CMV infection is associated with the progression of hypertension and hypertensive target organ damage (TOD) remains to be identified. We aimed to examine the relationship between CMV infection and the progression of hypertension and hypertensive TOD, which could provide clues on the possible mediating mechanisms, in the Han Chinese population. A total of 372 patients with hypertension and 191 healthy controls (Han participants from Xinjiang, China) were included in the study. Enzyme-linked immunosorbent assay (ELISA) and qPCR were used to detect CMV infection. C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) titers were also analyzed using an ELISA kit. Moreover, cardiovascular disease markers were evaluated by echocardiography, carotid ultrasonography, and tomographic scans. Essential hypertension (EH) patients exhibited a marked increase in CMV IgG antibody, CRP, TNF-α, and IL-6 levels. Higher grade of hypertension and hypertensive TOD had higher CMV IgG antibody and CRP levels. The CMV IgG antibody titers were positively correlated with arterial BP, greater grade of hypertension and hypertensive TOD, and CRP and IL-6 levels. The higher quartile of CMV IgG titer and CRP level were associated with the incidence of hypertension and the progression of hypertension and hypertensive TOD. In the Han Chinese population, high CMV IgG titers are associated with the progression of hypertension and hypertensive TOD. CMV IgG titer >4.25 U could be an independent predictor of hypertension and progression of hypertension, while that >4.85 U could be an independent risk factor for hypertensive TOD. The underlying mechanism may be largely mediated by chronic inflammation.

MicroRNA‑1929‑3p participates in murine cytomegalovirus‑induced hypertensive vascular remodeling through Ednra/NLRP3 inflammasome activation

“…However, the degree of MCMV infection at 9 months of age was significantly lower compared with that at 12 months of age. This finding was consistent with our previous population survey, which found that an increase in HCMV IgG titer was an independent risk factor for EH and target organ damage during HCMV infection ( 48 ). Another important reason may be that elevated blood pressure is a hemodynamic factor that induces vascular remodeling ( 49 ).…”

Screening and validation of differentially expressed microRNAs and target genes in hypertensive mice induced by cytomegalovirus infection

“…Our previous studies found that HCMV infection is associated with EH in patients of Kazakh and Han ethnicity in Xinjiang, and is associated with EH progression and target organ damage in patients of Han ethnicity, further supporting the correlation between HCMV and hypertension (24,25). We thus hypothesized that MCMV may be correlated to hypertension in mice through similar miRNA-induced mechanisms.…”

“…MicroRNAs (miRNAs) are highly conserved, single-stranded, non-coding small RNAs (19)(20)(21)(22)(23)(24)(25) nucleotides in length) that negatively regulate the expression of their target genes at the post-transcriptional level, by directly binding to the 3'-untranslated region (UTR) or 5'-untranslated region of their target mRNAs (19,20). Previous studies have shown that several miRNAs are involved in the development of primary hypertension (21,22).…”

Cytomegalovirus-specific CD8+ T-cell responses are associated with arterial blood pressure in people living with HIV

“…provided evidence of a relationship between CMV-specific immune responses and elevated blood pressure or arterial stiffness [22,[27][28][29][30]. However, no previous studies have investigated the relationship between blood pressure and CMV-specific T-cell immunity in PLHIV.…”

“…CMV has been linked to increased risk of CVD-related morbidity and mortality in PLHIV [16], and increased magnitude of CMV-specific immune responses have been associated with subclinical cardiovascular disease [17][18][19]. The relationship between CMV-specific immune responses and risk of CVD has been thoroughly described in the general population [20][21][22][23][24][25][26][27][28][29][30], where CMV-specific immune responses are associated with risk of hypertension [22,[27][28][29][30], and CMV-specific T-cells have been shown to have a direct effect on the vascular endothelium [27,[31][32][33][34]. Thus, the relationship between CMV and adverse CVD-outcomes is not a unique feature of HIV infection, but may be increasingly relevant in this population due to high prevalence of CMV in PLHIV, higher immune responses against CMV, and increasing life expectancy leading to a higher lifetime CMV exposure in PLHIV.…”