Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets

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.

Keywords

oxidative stress / mitoK_ATP / mPTP / HIF-1α / mitochondrion / heart ischemia

Fundings

This work was supported by "Potential Medicinal Plants of Uzbekistan with Adaptogenic Effects and Their Molecular, Cellular, and Therapeutic Mechanisms" from the Innovative Development Agency under the Ministry of Higher Education, Science, and Innovation of the Republic of Uzbekistan (Grant No. FL-8323102109).

Acknowledgments

We would like to express our sincere gratitude to Alfraganus University for their valuable contributions to this work.

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