Journal Article Ppublish 1 citation
PubMed: 40122680 DOI: 10.7555/JBR.38.20240387
Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets.
J Biomed Res 39(3):254-269
Authors: Izzatullo Abdullaev, Ulugbek Gayibov, Sirojiddin Omonturdiev, Sobirova Fotima, Sabina Gayibova, Takhir Aripov
Affiliations
- A. S. Sadykov Institute of Bioorganic Chemistry, Science Academy of Uzbekistan, Laboratory of Plant CytoProtectors, Tashkent 100007, Uzbekistan.
- Alfrganus University, Faculty of Medicine, Department of Pharmacy and Chemistry, Tashkent 100190, Uzbekistan.
Abstract
Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases, including ischemia, heart failure, and hypertension. Under hypoxia, oxygen deficiency disrupts oxidative phosphorylation in mitochondria, impairing ATP production and generating reactive oxygen species (ROS). These reactive species induce mitochondrial dysfunction, leading to oxidative stress, calcium imbalance, and activation of apoptosis pathways. The mitochondrial ATP-sensitive potassium channel (mitoK ATP) and mitochondrial permeability transition pore (mPTP) channels are particularly affected, contributing to membrane potential loss, cytochrome c release, and cell death. This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases, with a focus on mitochondrial impairment, ion channel dysfunction, and ROS overproduction. Additionally, we examine hypoxia-inducible factor 1-alpha (HIF-1α) as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress. Antioxidants and compounds modulating key ion channels, such as mitoK ATP and mPTP, are highlighted as promising interventions for mitigating hypoxia-induced damage. Furthermore, we emphasize the potential of integrating in vitro, in vivo, and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.
MeSH
Cells, Stress, Physiological, Cardiovascular Diseases, Mitochondria, Oxidative Stress, Biomarkers, Ion Channels, Hypoxia, Therapeutics, Mitochondrial Permeability Transition Pore