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

Yuji Shimizu,Yasuhiro Nagata,Mami Tamai,Yuko Noguchi,Hirotomo Yamanashi,Shin-Ya Kawashiri,Kazuhiko Arima,Takahiro Maeda

doi:10.1186/s12199-021-00938-0

Abstract

BackgroundHuman T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60–99 years participating in a general health check-up.MethodsLogistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway.ResultsHTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]).ConclusionAsymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.

Highlights

Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway
Association between HTLV-1 and hypertension HTLV-1 infection was significantly associated with hypertension in an inverse manner (Model 1)
Association between platelet and hypertension by HTLV-1 infection status significant positive associations between platelets and hypertension were observed for non-HTLV-1infected subjects, no significant associations were observed for HTLV-1-infected subjects (Table 3)

Summary

Introduction

Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Since HTLV-1 possesses a characteristic of enhancing inflammation [10, 11] possibly by activating the NF-κB pathway [12], its biochemical characteristics might have an influence on endothelial maintenance, including hypertension and atherosclerosis progression. Single nucleotide polymorphisms (SNPs) in breast cancer suppressor BRCA1-associated protein (BRAP) activate an inflammatory cascade via the activation of the NF-κB pathway [13] and increase the risk of carotid atherosclerosis [14], while reducing the risk of hypertension [15, 16]. Since activation of the NF-κB pathway promotes the production of platelet activation proteins [19], HTLV-1 infection could be inversely associated with hypertension by activating platelet production, resulting in the progression of atherosclerosis

Methods

Results

Discussion

Conclusion