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<sub>ATP</sub>) 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<sub>ATP</sub> and mPTP, are highlighted as promising interventions for mitigating hypoxia-induced damage. Furthermore, we emphasize the potential of integrating <italic>in vitro</italic>, <italic>in vivo</italic>, and <italic>in silico</italic> studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.