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Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome
Hui Yu, Yun Zhou, Yu Duan, Yunlong Gao, Ning Fang, Jiawei Zhang, Yue Li
2021, 1(2): 95-101. doi: 10.2478/fzm-2021-0012
Keywords: cold exposure, blood pressure, NLRP3, tranilast

Objective: Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results: Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1℃), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1℃). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion: TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

TIE1 is a potential target for hypertension-related atrial fibrillation
Hui Yu, Longfei Hao, Rui Wang, Yongtai Gong, Yue Li
2026, 6(2): 86-96. doi: 10.1515/fzm-2026-0009
Keywords: hypertension, atrial fibrillation, TIE1
  Objective  Cardiovascular diseases pose a major public health challenge in China, particularly in northern frigid regions where environmental stressors and limited access to healthcare access exacerbate disease risk. Both atrial fibrillation (AF) and hypertension are influenced by cold exposure. AF is a frequent cardiovascular complication of hypertension, yet their causal relationship remains incompletely defined. This study aimed to elucidate the mechanisms linking hypertension to AF in frigid regions, with an emphasis on identifying key genes driving disease progression.  Methods  We analyzed clinical data from 29,786 patients hospitalized at the First Affiliated Hospital of Harbin Medical University. Multivariate logistic regression was used to assess the association between hypertension and AF, and Mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) datasets. Whole-blood expression quantitative trait locus (eQTL) analysis and pathway enrichment were applied to identify hypertension-related genes. Single-cell RNA sequencing data from AF patients and hypertensive rat models were used to validate the role of TIE1. In addition, gut microbiota GWAS data were integrated to explore microbial influences on hypertension.  Results  Hypertension emerged as both an independent and causal risk factor for AF in frigid regions. Gene expression analyses identified TIE1 as a central mediator of hypertension-related effects, with elevated cardiomyocyte TIE1 expression associated with increased susceptibility to AF. In hypertensive rats, increased TIE1 expression correlated with higher AF incidence and enhanced inflammatory cytokine production, whereas cardiomyocyte-specific TIE1 knockdown reduced AF occurrence and attenuated atrial remodeling. Gut microbiota analysis further revealed that the abundance of Adlercreutzia was inversely correlated with TIE1 expression, suggesting a potential protective role mediated through microbial regulation of host gene expression.  Conclusion  These findings establish a causal link between hypertension and AF in cold northern regions and identify TIE1 as a pivotal mediator of this association. Targeting TIE1 may represent a therapeutic strategy for hypertension-associated AF. Moreover, the identification of Adlercreutzia as a modulator of TIE1 underscores the potential of the gut microbiota in preventing cardiovascular complications in frigid regions and opens promising avenues for future interventions.