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Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
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Updated: Aug 7, 2025

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Urine Cell Transcriptomes Implicate Specific Renal Inflammatory Pathways Associated With Difficult-to-Control

Kausik Umanath1,2,3, Ruicong She4,5, Clare Hassett1

  • 1Division of Nephrology and Hypertension Henry Ford Health Detroit MI.

Journal of the American Heart Association
|March 9, 2023
PubMed
Summary
This summary is machine-generated.

Difficult-to-control hypertension in humans is linked to renal inflammation. Gene expression in urine-shed cells reveals inflammatory pathways, offering new insights into hypertension resistance.

Keywords:
RNA‐Seqgene expressionhypertensioninflammationpathway analysis

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Area of Science:

  • Nephrology
  • Genomics
  • Immunology

Background:

  • Renal mechanisms in human hypertension and treatment resistance are poorly understood.
  • Animal studies suggest chronic renal inflammation contributes to hypertension.
  • This study investigates cells shed in first-morning urine from hypertensive individuals with difficult-to-control blood pressure (BP).

Purpose of the Study:

  • To identify transcriptome-wide associations with BP in shed urinary cells.
  • To analyze nephron-specific genes and identify activated signaling pathways in difficult-to-control hypertension.
  • To understand the role of renal inflammation in resistant hypertension.

Main Methods:

  • Bulk RNA sequencing was performed on cells shed in first-morning urine from 47 participants of the Systolic Blood Pressure Intervention Trial (SPRINT).
  • Participants were divided into "BP-difficult" (n=29) and "easy-to-control BP" (n=18) groups based on BP control and medication use.
  • Bioinformatic approaches were used to identify differentially expressed genes and activated signaling pathways.

Main Results:

  • 60 differentially expressed genes (>2-fold change) were identified in the BP-difficult group.
  • Upregulated genes in the BP-difficult group included Tumor Necrosis Factor Alpha Induced Protein 6 and Serpin Family B Member 9, associated with inflammation.
  • Pathway analysis revealed overrepresentation of inflammatory networks, including interferon signaling and granulocyte adhesion and diapedesis (P<0.001).

Conclusions:

  • Transcriptomes from shed urinary cells can identify a gene expression profile associated with difficult-to-control hypertension.
  • This profile is linked to renal inflammation, suggesting its role in hypertension resistance.
  • Findings provide novel insights into the molecular mechanisms underlying resistant hypertension.