Obstructive sleep apnea (OSA) is a respiratory condition during sleep caused by repeated pauses in breathing due to upper airway obstruction. It is estimated that OSA affects 30% of the population, but only 10% are well diagnosed due to the absence of a well-defined symptomatology and poor screening tools for early diagnosis. OSA is associated to an endothelial dysfunction inducing several biological responses such as hypoxia, hypercapnia and oxidative stress, among others. OSA also triggers respiratory, nervous, metabolic, humoral and immunity system activations that increase the possibility of suffering a cardiovascular (CV) disease. In this review, we expose different studies that show the relationship between OSA and endothelial dysfunction and its association with CV pathologies like hypertension, and we define the most well-known treatments and their limitations. Additionally, we describe the potential future directions in OSA research, and we report clinical features such as endothelial progenitor cell alterations that could act as biomarkers for the development of new diagnostic tools and target therapies.

Pulmonary hypertension (PH) is a progressive disease characterized by elevated artery pressures and pulmonary vascular resistance. Underlying mechanisms comprise endothelial dysfunction, pulmonary artery remodeling and vasoconstriction. Several studies have shown evidence of the critical role of oxidative stress in PH pathophysiology. Alteration of redox homeostasis produces excessive generation of reactive oxygen species, inducing oxidative stress and the subsequent alteration of biological molecules. Exacerbations in oxidative stress production can lead to alterations in nitric oxide signaling pathways, contributing to the proliferation of pulmonary arterial endothelial cells and smooth muscle cells, inducing PH development. Recently, antioxidant therapy has been suggested as a novel therapeutic strategy for PH pathology. However, the favorable outcomes observed in preclinical studies have not been consistently reproduced in clinical practice. Therefore, targeting oxidative stress as a therapeutic intervention for PH is an area that is still being explored. This review summarizes the contribution of oxidative stress to the pathogenesis of the different types of PH and suggests antioxidant therapy as a promising strategy for PH treatment.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the presence of organized clots obstructing the pulmonary arteries. Pulmonary endarterectomy (PEA) is the standard treatment, but in cases of inoperability, Riociguat, a soluble guanylate cyclase (sGC) stimulator, is the only approved pharmacological option. Endothelial dysfunction (ED) plays a central role, with the NO/sGC/cGMP pathway being critically involved. The aim of this study is to identify the molecular pathways contributing to ED and assess the therapeutic potential of Riociguat, BAY 60-2770, and Sildenafil in reinstating vascular homeostasis. Endothelial cells (ECs) were isolated from PEA specimens of individuals diagnosed with CTEPH (CTEPH-EC). ECs derived from healthy pulmonary arteries (HPAECs) were used as controls. Cells were treated with different concentrations of Riociguat, BAY-60-2770 and Sildenafil, followed by functional assays, transcriptomic, and molecular analyses. The drugs used induced significant effects on endothelial cell dynamics, including decreased proliferation, increased apoptosis, and enhanced angiogenesis both in vitro and in vivo. Transcriptomic analysis followed by validation studies identified significant alterations in genes related to angiogenesis, with marked changes observed following BAY 60-2770 treatment. Dysregulation in the ERK/eNOS/PKG signaling pathway was demonstrated in CTEPH-EC compared to HPAEC at both the gene and protein level. Treatment with Riociguat and Sildenafil restored ERK/eNOS, but not PKG signaling. Therapeutic approaches targeting endothelial dysfunction and the NO/sGC pathway in CTEPH partially restore endothelial function, highlighting the dual action of Riociguat and Sildenafil, stimulating sGC while exerting upstream effects by enhancing eNOS signaling. These findings underscore the importance of targeted pharmacological approaches to improve patient outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant global morbidity since 2019. Long COVID, characterized by persistent symptoms after acute infection, may involve endothelial injury. We analyzed endothelial colony-forming cells (ECFCs) from post-COVID-19 patients at 3- and 6-month post-infection, comparing them with healthy controls and stratifying by prior pulmonary embolism (PE). Transcriptomic profiling identified differentially expressed genes (DEGs) associated with endothelial homeostasis, inflammation, oxidative stress, and thrombosis. Post-COVID ECFCs showed downregulation of NOS3, KLF2, ANGPT1, PIK3R3, GBX2, GDF6, SMAD6, SRC, and TGFB1, and upregulation of CASP1, CXCL5, IL12A, SOD2, TIMP3, and TLR2. Minimal differences were observed between 3 and 6-month samples. PE patients showed downregulation of thrombosis-related genes such as PTGS2 and ACKR3. These findings indicate sustained endothelial dysfunction and inflammation up to 6 months post-infection, highlighting the importance of long-term monitoring and potential therapeutic strategies to support vascular health in post-COVID-19 patients.

Introduction: SARS-CoV-2 infection causes severe endothelial damage, an essential step for cardiovascular complications including coagulopathies and thromboembolisms. Endothelial progenitor cells (EPCs) could act as a biomarker of vascular damage but its role in SARS-CoV-2 is unknown. Objectives: The study aims to quantify the number of EPCs at 3 and 6 months after SARS-CoV-2 infection and to assess whether the number of EPCs differs from COVID-19 patients who suffered an acute pulmonary embolism (PE) than those that did not. Moreover, it will be evaluated if this increase correlates with any of the clinical parameters studied. Materials and Methods: A total of 22 patients were recruited in the study at different time points after overcoming COVID-19 (3 and 6 months) and 26 healthy controls. All subjects were matched for age, gender, BMI and clinical comorbidities. Of these 22 COVID-19 patients, 9 had suffered PE. EPCs were obtained from peripheral blood and cultured with specific medium and conditions. The appearance, number of colonies and days of appearance were quantified. Results: The results show an abnormal increase in the number of EPCs at 3 and 6 months post-infection compared to controls. There was no difference in EPCs production in post-COVID-19 patients who presented an acute PE compared to those that did not. Non-PE patients with higher levels of D dimer showed significant higher troponin levels at 6 months compared to PE patients. No correlation was found between troponin levels and the number or appearance of EPCs colonies or with any other clinical parameter studied. Conclusion: The results confirm the presence of vascular sequelae in post-COVID-19 patients that is maintained for up to 6 months.