HLA-B and TIMP1 as hub genes of the ventricular remodeling caused by hypertension

Aging (Albany NY). 2024 May 9;16(9):8260-8278. doi: 10.18632/aging.205816. Epub 2024 May 9.

Abstract

Rationale: Myocardial fibrosis is an important pathological change that occurs during ventricular remodeling in patients with hypertension and is an important pathophysiological basis of cardiovascular disease. However, the molecular mechanism underlying this ventricular remodeling is unclear.

Methods: Bioinformatics analysis identified HLA-B and TIMP1 as hub genes in the process of myocardial fibrosis. Expression and correlation analyses of significant hub genes with ventricular remodeling were performed. Weighted gene co-expression network analysis (WGCNA) was performed to verify the role of HLA-B. ceRNA network was constructed to identify the candidate molecule drugs. Receiver operating characteristic (ROC) curves were analyzed.

Results: RT-qPCR was performed to verify the roles of HLA-B and TIMP1 in seven control individuals with hypertension and seven patients with hypertension and ventricular remodeling. The WGCNA showed that HLA-B was in the brown module and the correlation coefficient between HLA-B and ventricular remodeling was 0.67. Based on univariate logistic proportional regression analysis, HLA-B influences ventricular remodeling (P<0.05). RT-qPCR showed that the relative expression levels of HLA-B and TIMP1 were significantly higher in HLVR samples compared with their expression in the control group.

Conclusions: HLA-B and TIMP1 might provide novel research targets for the diagnosis and treatment of HLVR.

Keywords: HLA-B; hypertension; myocardial fibrosis; significant module; ventricular remodeling.

MeSH terms

  • Aged
  • Computational Biology
  • Female
  • Fibrosis / genetics
  • Gene Regulatory Networks
  • HLA-B Antigens* / genetics
  • Humans
  • Hypertension* / genetics
  • Male
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-1* / genetics
  • Tissue Inhibitor of Metalloproteinase-1* / metabolism
  • Ventricular Remodeling* / genetics

Substances

  • TIMP1 protein, human