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Related Experiment Video

Updated: Jan 13, 2026

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
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Integrated Stress Response (ISR) Modulators in Vascular Diseases.

Alexander Kalinin1,2, Ekaterina Zubkova1, Irina Beloglazova1

  • 1National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Ministry of Health of the Russian Federation, Moscow 121552, Russia.

Cells
|January 9, 2026
PubMed
Summary
This summary is machine-generated.

The integrated stress response (ISR) plays a dual role in vascular diseases. Understanding its context-dependent effects offers new therapeutic strategies for cardiovascular conditions.

Keywords:
GCN2PERKPKRcardiovascular diseasesintegrated stress responsepulmonary arterial hypertensionpulmonary capillary hemangiomatosispulmonary veno-occlusive diseaserestenosisthrombosis

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Area of Science:

  • Vascular Biology
  • Molecular Mechanisms
  • Signaling Networks

Background:

  • Vascular dysfunction drives cardiovascular diseases, the leading cause of death globally.
  • Limited therapeutic options stem from an incomplete understanding of vascular pathology mechanisms.
  • The integrated stress response (ISR) is an understudied signaling network in vascular biology.

Purpose of the Study:

  • To review the roles of core ISR kinases (PERK, GCN2, HRI, PKR) in vascular homeostasis and pathology.
  • To present a framework for the ISR as a context-dependent "double-edged sword" in vascular diseases.
  • To discuss pharmacological ISR modulators and their therapeutic potential.

Main Methods:

  • Review of existing literature on ISR kinases in vascular biology.
  • Analysis of ISR roles in atherosclerosis, pulmonary hypertension, and angiogenesis.
  • Discussion of pharmacological modulators and preclinical findings.

Main Results:

  • ISR kinases have dual roles: PERK and PKR promote inflammation and apoptosis, while GCN2 is protective.
  • ISR outcomes depend on cell type, stress, and downstream signaling bias (ATF4 vs. CHOP).
  • Pharmacological ISR modulators show promise in preclinical models by reducing inflammation and apoptosis.

Conclusions:

  • The ISR is a critical regulatory node in vascular pathophysiology.
  • Selective, context-aware modulation of the ISR is a potential therapeutic strategy for vascular diseases.
  • Targeting the ISR may offer novel treatments for atherosclerosis, pulmonary hypertension, and other cardiovascular conditions.