Endothelial dysfunction plays a central role in the pathogenesis of cardiovascular diseases, driven by a complex interplay of oxidative stress, metabolic imbalances, and adipokine dysregulation. Excessive reactive oxygen species reduce nitric oxide bioavailability by impairing endothelial nitric oxide synthase function, leading to vascular inflammation and impaired vasodilation. Adipose tissue-derived hormones such as leptin, adiponectin, and resistin exert opposing effects on vascular homeostasis, influencing inflammation and oxidative stress in obesity and metabolic syndrome. Dyslipidemia, particularly through oxidized LDL, initiates endothelial injury and foam cell formation, accelerating atherosclerosis. Furthermore, hypertension and obesity exacerbate vascular dysfunction by disrupting the balance between vasodilators and vasoconstrictors, enhancing oxidative stress, and altering perivascular adipose tissue function. These interrelated mechanisms contribute to the progression of atherosclerotic cardiovascular disease and diabetic vascular complications. A deeper understanding of these processes is essential for developing targeted interventions to restore endothelial health and reduce cardiometabolic risk.

Oxidative stress, caused by an imbalance between the production of reactive oxygen species and endogenous antioxidant capacity, is a key etiological factor in numerous pathologies, including neurodegenerative and cardiovascular diseases. The limited clinical efficacy of conventional antioxidants is primarily due to their insufficient accumulation within the mitochondria, the main site of intracellular ROS generation. This article reviews the design and application of Mitochondria-Targeted Antioxidants, which represent a major advance in precision medicine. The design of these compounds involves linking an antioxidant “payload” to a lipophilic cation, such as the triphenylphosphonium group. This positive charge leverages the negative electrochemical gradient across the inner mitochondrial membrane to drive the antioxidant into the organelle. This mechanism allows the drug to reach concentrations over 100 times higher than non-targeted alternatives. The discussion encompasses the structure-activity analysis of the carrier, the payload (e.g., quinone derivatives), and the linker, which determine optimal subcellular partitioning and scavenging efficiency. Preclinical data highlight the therapeutic potential of this approach, showing strong neuroprotection in models of Parkinson’s and Alzheimer’s diseases, as well as improved outcomes in cardiovascular and ocular health. By restoring redox balance specifically within the mitochondria, these targeted therapies offer a more effective way to treat chronic oxidative damage.

Acute kidney injury (AKI), chronic kidney disease (CKD), and diabetic kidney disease (DKD) are interconnected disorders linked by shared mechanisms involving redox imbalance and mitochondrial dysfunction. This review summarizes current evidence on the role of excessive reactive oxygen species (ROS) production, impaired oxidized nicotinamide adenine dinucleotide (NAD⁺) metabolism, altered mitochondrial bioenergetics, disrupted mitochondrial dynamics, and defective mitochondrial quality control pathways, including mitophagy and the mitochondrial unfolded protein response (UPR^mt), in kidney disease progression. Experimental and clinical studies indicate that these mechanisms contribute to inflammation, fibrosis, apoptosis, and maladaptive repair, promoting progression from AKI to CKD and worsening DKD. The review also discusses emerging biomarkers and therapeutic strategies targeting oxidative stress and mitochondrial dysfunction. Overall, redox-mediated mitochondrial injury represents a shared pathogenic axis and a potential therapeutic target across kidney diseases.

Background: Cardiovascular diseases (CVDs) remain the leading global cause of mortality, yet a critical “translational gap” persists: Conventional biomarkers often fail to detect subclinical stages or predict individual disease trajectories. While single-omics studies have proliferated, the field lacks a unified framework synthesizing these molecular layers with advanced computational intelligence. Aim: This review addresses this gap by evaluating the synergistic integration of multi-omics and Artificial Intelligence (AI) to transition from descriptive markers toward predictive precision cardiology. Scope: Evidence from non-coding RNA networks (miRNAs, lncRNAs) and exosomal trafficking is synthesized alongside a critical assessment of Machine Learning (ML) architectures, including supervised, unsupervised, and deep learning (DL) models. Findings: Unlike traditional reviews, this work delineates the specific pipelines required to deconvolute high-dimensional signatures—such as TMAO, acylcarnitines, and cardiac-enriched miRNAs—into actionable risk models for heart failure (HF) and post-infarction outcomes. The primary barrier to clinical translation is identified not as data scarcity but as the lack of standardized bioinformatic workflows and model interpretability. Conclusions: This review distinguishes itself by proposing an integrated molecular–computational framework that prioritizes Explainable AI (XAI) and standardized multi-omic protocols. Such a shift is essential to bridge the gap between high-dimensional biological insights and routine clinical decision-making.