Search Results (1,216)

Background/Objectives: Pulmonary hypertension (PH) is an increasingly recognized complication in patients with end-stage renal disease (ESRD) undergoing hemodialysis, particularly those utilizing arteriovenous fistulas (AVF) or grafts (AVG) for vascular access. The prevalence and clinical impact of PH in this population remain unclear due to methodological heterogeneity and variable diagnostic criteria. This systematic review and meta-analysis aimed to quantify the association between AVF/AVG use and PH prevalence in ESRD patients and to explore sources of heterogeneity. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted for studies published through 31 December 2024, without language or date restrictions. Eligible studies included adults (≥18 years) with ESRD on dialysis, comparing those with AVF/AVG access to non-AVF/AVG controls (e.g., tunneled dialysis catheters or peritoneal dialysis), and reporting PH prevalence or mean pulmonary artery pressures. Study quality was assessed using the Newcastle–Ottawa Scale, and risk of bias was evaluated. A random-effects meta-analysis calculated pooled odds ratios (OR) for PH prevalence, with heterogeneity assessed by I² and Cochran’s Q. Sensitivity analyses and tests for publication bias (Egger’s and Begg’s) were performed. Secondary analysis compared pooled mean pulmonary artery pressures between groups. Results: Eleven observational studies (1299 dialysis patients) met the inclusion criteria; ten studies (1224 patients) contributed to the quantitative meta-analysis after exclusion of one study with a zero-event control arm. Most studies were small, predominantly cross-sectional, and of moderate methodological quality. The pooled analysis showed a statistically significant association between AVF/AVG use and PH (OR 2.06, 95% CI: 1.69–2.52), with low statistical heterogeneity (I² = 0%). This estimate was sensitive to individual studies: in leave-one-out analysis the association lost statistical significance when the single most influential study was removed indicating that the pooled result is driven in part by a small number of studies rather than being uniformly robust. No statistical evidence of publication bias was detected. Five studies reported continuous pulmonary artery pressures, which were directionally higher in AVF/AVG patients but were not pooled because of extreme heterogeneity (I² = 99.4%). Conclusions: In this synthesis of observational data, AVF/AVG use was associated with higher odds of pulmonary hypertension than non-AVF/AVG access. Because all included studies were observational and the pooled estimate is sensitive to individual influential studies, these findings indicate a possible association rather than a causal effect and should be interpreted with caution. They support the rationale for prospective hemodynamic studies and for evaluating—rather than presuming the benefit of—PH monitoring and individualized access strategies in higher-risk dialysis patients. Full article

The liver and lungs maintain an essential anatomical and physiological network crucial for systemic homeostasis. In the presence of cirrhosis, particularly when accompanied by portal hypertension, this intricate communication is disrupted. The resulting alterations can lead to a range of pulmonary complications through intertwined vascular, immunologic, and mechanical mechanisms that underscore the close relationship between these two organs. This review provides an overview of the liver–lung axis and summarizes current concepts of the pathophysiological processes by which advanced liver disease contributes to major respiratory complications. It also highlights diagnostic principles and clinical manifestations, with emphasis on hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. Although these conditions differ substantially in their underlying pathogenesis, they share common clinical consequences, including impaired arterial oxygenation, reduced functional capacity, and an increased risk of mortality prior to liver transplantation. In addition, the review explores the ongoing debate regarding the potential association between chronic hepatitis C virus infection and pulmonary fibrosis. Overall, early recognition of these pulmonary complications is crucial, as they have important implications for symptom burden, therapeutic decision-making, liver transplant eligibility, and overall clinical outcomes in patients with chronic liver disease. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and fibrosis involving the skin and internal organs. Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac involvement remain major causes of morbidity and mortality, yet prediction of disease progression and therapeutic responsiveness remains difficult. Methods: This narrative review summarizes studies of circulating blood biomarkers in SSc, with emphasis on literature published since 2020 and on Japanese multicenter longitudinal cohort studies. Disease-specific autoantibodies were intentionally excluded from the main scope, and the review focuses on soluble biomarkers measurable in peripheral blood that reflect inflammation, endothelial injury, and fibrotic remodeling. Results: Multiple cytokines, chemokines, adhesion molecules, endothelial markers, extracellular vesicle-associated molecules, and extracellular matrix (ECM)-related molecules have been associated with disease activity, organ involvement, prognosis, and therapeutic response in SSc. Clinically established biomarkers such as KL-6 and surfactant protein-D (SP-D) for SSc-associated interstitial lung disease (ILD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for pulmonary arterial hypertension (PAH), are already used as adjunctive tools in routine clinical assessment, whereas many other candidate biomarkers, including interleukin (IL)-6, CCL2, CXCL8, CXCL4, intercellular adhesion molecule-1 (ICAM-1), CCL18, periostin, endostatin, endothelin-1, extracellular vesicle signatures, and ECM turnover markers remain at varying stages of clinical validation. In particular, Japanese multicenter longitudinal studies have demonstrated the prognostic significance of circulating chemokines and adhesion molecules in early SSc and, more recently, identified biomarker-based clusters associated with distinct pulmonary trajectories. Recent multidimensional proteomic and transcriptomic approaches further support biologically based patient stratification in SSc. Conclusions: Blood biomarkers may contribute to risk stratification, prediction of organ progression, and future precision medicine in SSc. Integrated biomarker signatures may better capture the biological heterogeneity of SSc than single biomarkers alone. However, most candidate biomarkers still require external validation, assay standardization, and demonstration of incremental value over conventional clinical variables before routine clinical implementation. Full article

Hypoxic pulmonary hypertension (HPH) is a progressive vascular disease characterized by an abnormal increase in pulmonary arterial pressure resulting from pulmonary vasoconstriction and pulmonary vascular remodeling (PVR). Excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are key drivers of PVR. Caragana jubata (Pall.) Poir. (C. jubata), known as “zuomaoxing” in Tibetan medicine, is traditionally used to treat blood-related disorders. However, the potential preventive and therapeutic effects of C. jubata on HPH remain unclear. Here, we integrated in vivo pharmacology, serum pharmacochemistry, PASMC assays, DARTS-MS chemoproteomics, and pathway validation to investigate the effects of C. jubata ethanol extract (ECJ) on HPH-associated PVR and the effects of a serum-exposed candidate component on CoCl₂-induced PASMC activation. In HPH rats, ECJ reduced mean pulmonary arterial pressure and alleviated right ventricular hypertrophy and PVR. Serum pharmacochemistry detected 47 ECJ-derived serum-exposed features, including one prototype putatively annotated as ginkgolide J. Ginkgolide J attenuated CoCl₂-induced PASMC proliferation, Ki-67 positivity, and migration without significantly affecting PASMC viability. DARTS-MS identified 1235 ginkgolide J-associated protease-susceptibility candidate proteins, and pathway validation indicated that ginkgolide J suppressed CoCl₂-induced MEK1/ERK1/2 activation. These findings suggest that ECJ has potential value against HPH-associated PVR and that ginkgolide J is a candidate anti-proliferative compound in PASMCs. Full article

Introduction: Giant sinus of Valsalva aneurysms (SVA) represent a rare cardiovascular pathology that may remain asymptomatic for an extended period. However, they are associated with a high risk of life-threatening complications, including compression of adjacent structures and aneurysm rupture. Case presentation: We report a clinical case of a 71-year-old female patient with a long-standing history of arterial hypertension and cardiac arrhythmias, in which echocardiography revealed aneurysmal dilatation of the right coronary sinus. Cardiac computed tomography (CT) confirmed the presence of a giant aneurysm of the right sinus of Valsalva measuring 70 × 51 × 49 mm, compressing the outflow tracts of both ventricles (right—up to 7 mm, left—up to 8 mm) and the left inferior pulmonary vein (up to 3 mm), which clinically manifested as dyspnoea, lower-extremity oedema, and rhythm disturbances. The patient successfully underwent complex reconstructive surgery, including aortic root replacement and valve repair. Despite the technical success of the operation, the patient died from pneumonia three months postoperatively. Discussion: This observation underscores the critical role of imaging modalities (echocardiography and CT) in verifying this pathology. The use of multimodal imaging facilitated both a timely diagnosis and a detailed three-dimensional evaluation of the aneurysm’s relationship with adjacent structures. This information, in turn, guided personalised surgical planning. Conclusions: This case highlights the necessity of considering giant SVA in the differential diagnostic workup of patients who present with unexplained symptoms of heart failure. Full article

Background: Dynamic risk stratification is fundamental to the modern management of pulmonary arterial hypertension (PAH). However, data on the impact of sequential add-on therapy in patients with Group 1.4 PAH—particularly in Latin American populations—remains limited. This study evaluated changes in risk classification using COMPERA 2.0 and REVEAL Lite 2 scores in patients treated with endothelin receptor antagonist (ERA) and phosphodiesterase type 5 inhibitor (PDE5i) combination therapy (macitentan + sildenafil) at a referral center in Mexico. Methods: In this single-center, retrospective cohort study, 25 patients with a confirmed diagnosis of PAH between 1st January 2022 and 31st December 2024 were evaluated at baseline and after 24 weeks of treatment. Clinical, functional, and biochemical parameters were recorded. Within-patient changes were analyzed using the Wilcoxon signed-rank test, and agreement between risk assessment tools was assessed using Spearman’s correlation coefficient. Results: At 24 weeks, patients demonstrated significant improvement in World Health Organization functional class (p = 0.002) and a significant reduction in brain natriuretic peptide levels (p = 0.003). Both COMPERA 2.0 and REVEAL Lite 2 scores showed a consistent shift toward lower-risk categories. A strong concordance between the two tools was observed. Conclusions: Sequential add-on ERA + PDE5i therapy was associated with meaningful improvement in risk stratification among patients with Group 1.4 PAH. These findings support the clinical utility of simplified, noninvasive risk assessment tools in real-world settings, particularly in resource-constrained environments. Full article

Background and Objectives: Right heart failure is a life-threatening complication of pulmonary hypertension (PH), with limited treatment options. Although recombinant human brain natriuretic peptide (rhBNP) is widely used in left heart failure, its effectiveness in right heart failure associated with varying groups of PH (Groups 1, 2, and 4) is unknown. Materials and Methods: 763 patients with varying groups of PH (PH Groups 1, 2, and 4) were enrolled and received both conventional therapy and rhBNP treatment. Therapeutic efficacy and adverse event incidence were evaluated among the PH groups. Results: Significant reductions in variables reflecting cardiac congestion, including NT-proBNP, total bilirubin, and body weight, were observed in all PH subgroups (all p < 0.001). The median percentage changes were −47% (IQR −76 to −24), −21% (IQR −33 to −1), and −3% (IQR −7 to −1), respectively. Alanine transaminase levels presented a decreasing trend (p < 0.001), whereas creatinine levels remained unchanged (p > 0.05), with consistent trends across PH subgroups. The hemodynamic response was heterogeneous, with marked decreases in the mean arterial pressure in Groups 1 and 4 (p < 0.001) but not in Group 2. Improvement in dyspnea and edema of the lower limbs was observed in 49.9% and 66.6% of cases, respectively. The overall incidence of adverse events was 0.66%, with 0.26% (2/763) being serious, all of which were in Group 1 PH. Conclusions: Findings from this exploratory analysis indicated that rhBNP treatment was associated with favorable changes in congestive status and clinical symptoms across different PH subgroups, as well as stable end-organ function. Of note, all patients received comprehensive conventional background therapy; thus, these improvements cannot be exclusively attributed to rhBNP alone. Given the observed hemodynamic fluctuations, close blood pressure monitoring should be considered throughout the treatment course, particularly for patients in Groups 1 and 4, and most notably for high-risk PAH patients (Group 1 PH). Full article

Background and Objectives: Pulmonary sequestration (PS) is a rare congenital lung anomaly with anomalous systemic arterial supply. Surgical resection is the standard treatment, but some children have contraindications. Endovascular embolization (EE) is an established alternative; published pediatric experience is limited, particularly in neonates. We report a two-centre experience with extended follow-up and quantitative hemodynamic data. Methods: Six pediatric patients (five male; median age 6 months, range 11 days to 4 years and 8 months) underwent EE for PS at two centres in Gdańsk, Poland, between 2020 and 2025. Contraindications to surgery were severe pulmonary arterial hypertension, high-output cardiac failure, low body weight with comorbidity, complex extralobar anatomy or refused parental consent. Procedures were performed under general anesthesia via right common femoral arterial access; device strategy was tailored to vessel anatomy. Results: Technical success was 100% with no procedural complications. Median feeding-artery diameter was 3.4 mm (range 2.1 to 5.3 mm). An Amplatzer-family vascular plug was used in five patients (83.3%), pushable platinum coils in two (33.3%) and Onyx-18 in one (16.7%); two had hybrid combinations and one underwent planned staged two-step embolization. Median procedural duration was 51 min. At median follow-up of 50 months (range 11 to 68), all patients showed sequester regression on imaging. Reverse cardiac remodelling occurred within five weeks in the patient with pre-procedural left ventricular dilation (Z-score +2.45 returning to normal); systolic pulmonary artery pressure fell from 35 to 40 to 17 mmHg within six weeks in the neonate treated at 11 days of life for high-output cardiac failure. No patient required surgical resection. Conclusions: Endovascular embolization is safe and effective in pediatric patients with pulmonary sequestration and contraindications to surgery, including neonates with comorbidity. Documented reverse cardiac remodelling and rapid hemodynamic improvement support its use in selected cases. Full article

Pulmonary hypertension (PH) is a progressive, multifactorial syndrome characterized by elevated pulmonary arterial pressure and right heart dysfunction, associated with significant morbidity, impaired quality of life, and poor prognosis. Advances in classification, hemodynamic definitions, and targeted pharmacotherapies have improved understanding and management, yet therapeutic challenges persist across the five World Health Organization groups of PH. Historically, exercise was discouraged due to concerns about adverse hemodynamic effects, but growing evidence has suggested that structured, supervised training is safe and beneficial. Randomized trials and meta-analyses show improvements in six-minute walk distance, peak oxygen uptake, right ventricular function, ventilatory efficiency, and health-related quality of life, with a low incidence of adverse events. Physiological adaptations include favorable cardiac remodeling, enhanced endothelial function, improved skeletal and respiratory muscle performance, and improved neurohormonal activity. Despite this evidence, barriers such as patient fears, limited clinical expertise, and restricted access to specialized rehabilitation programs hinder widespread implementation. Current guidelines recommend supervised exercise as part of pulmonary rehabilitation for patients with stable PH, supporting its role as an adjunct to pharmacotherapy. This descriptive review briefly summarizes the pathophysiology of PH, phenotype-related differences and current therapeutic approaches, and the beneficial adaptations to exercise training, with the aim of informing exercise specialists and supporting safer, more effective integration of exercise-based rehabilitation into patient care. Full article

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disorder characterized by increased pulmonary vascular resistance and vascular remodeling. Genetic polymorphisms, epigenetic modifications, and ion channel dysregulation are increasingly recognized as key contributors to disease pathogenesis. Anoctamin-1 (ANO1/TMEM16A), a calcium-activated chloride channel, plays a critical role in vascular tone regulation. Objective: This study aimed to investigate the association between ANO1 gene polymorphisms (rs7127129 and rs2509153), promoter methylation status, and serum chloride levels in patients with idiopathic pulmonary arterial hypertension (IPAH), congenital heart disease (CHD), and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A total of 106 IPAH patients, 40 CHD patients, and 30 CTEPH patients, together with 125 healthy controls, were included. The control group had a comparable age distribution, with a balanced sex ratio, whereas females predominated in all three PH groups. Genotyping was performed using TaqMan-based real-time PCR. Promoter methylation was analyzed using bisulfite conversion followed by quantitative real-time PCR. Serum chloride levels were measured using an ion-selective electrode method. Results: No significant association was observed between rs7127129 and rs2509153 polymorphisms and IPAH or CTEPH (p > 0.05). However, rs7127129 showed a significant association with CHD (p < 0.05). After excluding hypertensive patients, both polymorphisms remained significantly associated with CHD. Serum chloride levels differed significantly among groups (p < 0.001), with higher levels observed particularly in the CTEPH and CHD groups compared to controls, while IPAH patients exhibited intermediate but still elevated levels relative to controls. In contrast, promoter methylation levels were significantly lower in all patient groups compared to controls. An inverse relationship between chloride levels and methylation status was observed. Conclusions: ANO1 polymorphisms are not major determinants of IPAH or CTEPH but may contribute to CHD susceptibility. Increased serum chloride levels, together with decreased promoter methylation, suggest a potential mechanistic link between ion channel dysregulation and epigenetic alterations in pulmonary hypertension. Further large-scale and functional studies are warranted. Full article

Background: Penetrating keratoplasty (PK) is a technically demanding corneal transplant procedure frequently performed in elderly patients with substantial systemic comorbidities. In this population, an anesthetic strategy that ensures hemodynamic stability, cooperative sedation, adequate analgesia, and preserved spontaneous ventilation is highly desirable. Dexmedetomidine, a highly selective alpha2-adrenergic agonist, provides “cooperative” sedation with minimal risk of respiratory depression and additional sympatholytic benefits. Methods: This single-center retrospective observational case series included 50 consecutive patients (American Society of Anesthesiologists [ASA] II–III, age 50–90 years) undergoing PK under sub-Tenon block combined with continuous dexmedetomidine infusion. Dexmedetomidine was administered without a loading bolus at 0.7 mcg/kg/h for 10–15 min, then reduced to 0.5 mcg/kg/h, targeting a Ramsay Sedation Scale (RSS) score of 2–3. The sub-Tenon block was performed using a mixture of levobupivacaine 0.5% and lidocaine 2% (3–5 mL). Heart rate (HR), mean arterial pressure (MAP), oxygen saturation (SpO₂) and RSS were recorded in nine predefined perioperative phases. Data were analyzed descriptively. Results: The mean age was 72 ± 9 years; 52% of patients were ASA III. Hypertension was present in all patients; 30% had cardiovascular disease, 28% diabetes mellitus type II, and 30% chronic obstructive pulmonary disease. Progressive, controlled bradycardia was observed (mean HR decreased from 76 to 57 beats/min during graft transplantation), while MAP gradually decreased from hypertensive baseline values (150–160 mmHg) to an optimal intraoperative range of 115–130 mmHg, without episodes of clinically significant hypotension. SpO₂ remained stable at 98–99% throughout all phases, with no episodes of desaturation or need for airway intervention or supplemental oxygen. Target sedation (RSS 2–3) was achieved in all patients (median RSS 3), with preserved spontaneous breathing and cooperation. Sub-Tenon block-related bulging occurred in 6% of cases. No episodes of clinically significant bradycardia, malignant arrhythmia, respiratory compromise, or need to discontinue dexmedetomidine were recorded. No opioids or non-steroidal analgesics were required intraoperatively or in the early postoperative period. Conclusions: The combination of sub-Tenon block and continuous dexmedetomidine sedation without a loading bolus represents a hemodynamically stable and respiratory-safe anesthetic strategy for PK in elderly, high-risk patients. These preliminary, hypothesis-generating findings suggest that the protocol provides stable surgical conditions and a favorable safety profile, justifying future prospective randomized controlled trials to establish its comparative efficacy against general anesthesia or standard sedative regimens. Full article

Local immune cell activation and vascular remodelling are characteristic pathogenic features of pulmonary arterial hypertension (PAH). HIV and schistosome infections have been individually associated with PAH. However, whether co-infection with these pathogens has a distinct impact on the development of pulmonary vascular disease remains poorly understood, partly due to the lack of experimental animal models. In a novel non-infectious model of HIV and Schistosoma pulmonary co-exposure based on lung embolisation of S. mansoni eggs in HIV-transgenic (HIV) mice, we previously reported exacerbated endothelial remodelling and dysfunction, along with increased pulmonary arterial pressure; which were associated with a unique profile of pro-inflammatory cytokines in the lung. In the present study, we used flow cytometric analysis of isolated lung leukocytes and immunofluorescence staining to characterise the pulmonary immune cell landscape associated with individual or combined exposure to HIV and schistosome. Compared with mice exposed to HIV (untreated HIV mice) or schistosome (egg-treated wild-type mice), co-exposed (egg-treated HIV mice) animals showed significantly increased numbers of interstitial and alveolar macrophages, patrolling-type monocytes, NKT and γδ T cells, and reduced CD8⁺ αβ T cells. Other lung immune cells, including inflammatory-type monocytes, eosinophils/neutrophils, dendritic cells, CD4⁺ αβ T cells, NK cells and B cells were not significantly affected in the co-exposure condition. Taken together, these results show for the first time that combined pulmonary exposure to HIV and Schistosoma, as it may occur in co-infected individuals, alters the local immune cell landscape in a manner distinct from that of individual exposure. Furthermore, these findings may contribute to a better understanding of the complex inflammatory processes involved in the pathogenesis of PAH, thereby supporting the development of therapies targeting pathogenic immune cells in pulmonary vascular disease associated with HIV and Schistosoma co-morbidity. Full article

Purpose: Acute ischemic stroke (AIS) is the most prevalent stroke subtype. Given the brain–heart interaction, this study investigated the association between cardiac parameters on admission routine preoperative chest CT and recanalization following thrombectomy in AIS patients. Method: We retrospectively analyzed 215 AIS patients (August 2018–June 2022) who underwent admission of none contrast chest computed tomography (NCCT) and thrombectomy within 24 h. Successful recanalization was defined as modified Treatment in Cerebral Ischemia (mTICI) score 2b-3. Multivariable logistic regression identified independent predictors. A nomogram was developed and validated using ROC, calibration, and decision curve analyses. Result: The cohort had a median age of 72 years; 63.7% were male. Hypertension (65.1%), atrial fibrillation (25.1%), and pleural effusion (56.3%) were prevalent. Successful recanalization occurred in 172 patients (80%). Independent predictors included mean arterial pressure (OR: 1.022, CI: 1.003–1.041, p = 0.025), left pulmonary artery diameter (OR: 0.838, CI: 0.733–0.958, p = 0.010), RV/A ratio (standardized) (OR:1.908, CI: 1.293–2.817, p = 0.001), septal angle (OR: 1.055, CI: 1.018–1.094, p = 0.004), and intraventricular septal angle (OR: 0.973, CI: 0.952–0.995, p = 0.015). The model achieved an AUC of 0.774 (p < 0.001) with strong calibration and net benefit. Conclusions: Cardiac parameters on routine preoperative chest CT correlate with recanalization following thrombectomy in AIS patients. The developed nomogram offers a reliable tool for clinical risk stratification. Full article

Background/Objectives. Pulmonary arterial hypertension (PAH) is a rare but severe disease which leads to right ventricular (RV) maladaptation, failure and death. Currently approved drugs have limited impact on disease progression. A multitarget strategy consisting of adenosine A₂B receptor activation and phosphodiesterase-4 (PDE4) inhibition, combined with human mesenchymal stromal cells (hMSCs) therapy, was tested in experimental PAH. The main objective was to determine whether the combination improved pulmonary hemodynamics, vascular remodeling, and RV function, given the limited disease-modifying effects of currently approved vasodilators. Methods. Vascular reactivity was assessed in isolated rat pulmonary artery rings exposed to the dual-target compound (LASSBio-1860) alone or in the presence of either ZM-241385 or MRS-1706. PAH was induced in male Wistar rats with monocrotaline (MCT, 60 mg·kg⁻¹) and confirmed by a decrease in pulmonary artery acceleration time to ejection time ratio (PAAT/TET). Animals were randomized to receive vehicle, hMSC (single i.v. dose, 1 × 10⁵ cells), LASSBio-1860 (62 mg·kg⁻¹·day⁻¹, p.o., 14 days), or their combination. Outcomes included PAAT/TET and RV cardiac output (RV-CO) by echocardiography, RV systolic pressure (RVSP) by direct puncture, Fulton index and RV wall thickness, lung histology (perivascular cell counts and wall thickness), and RV protein expression (TGF-β, CaMKII) by Western blot. Results. LASSBio-1860 produced endothelium-independent vasorelaxation of rat pulmonary arteries, consistent with A₂B agonism and PDE4 inhibition. In MCT-induced PAH, combination of LASSBio-1860 and hMSCs resulted in recovery of PAAT/TET and RV-CO, decrease in RVSP, RV hypertrophy, vascular inflammation and remodeling by downregulation of ventricular TGF-β and CaMKII. Conclusions. Combination of LASSBio-1860 with hMSC improved RV function, attenuated pulmonary hypertension, RV and vascular remodeling, and reduced inflammatory/proliferative signaling in MCT induced-PAH, supporting a promising multitarget therapeutic strategy for PAH. Full article

Endothelial dysfunction is a key characteristic of many diseases, including atherosclerosis, hypertension, heart failure, stroke, cancer, acute respiratory distress syndrome (ARDS), peripheral vascular disease, coronavirus 2019 (COVID-19), and pulmonary arterial hypertension (PAH). To improve understanding of the roles of endothelial cells (ECs) in health and disease, EC-specific genome editing technologies have been developed in recent years. Therapeutic strategies that aim to restore a healthy endothelial monolayer include the inhibition of endothelial genes that cause EC injury and dysfunction and the induction or activation of endothelial genes that drive EC repair and regeneration. In this review, we describe established recombinase-mediated genetic modification technologies and emerging EC-specific genome editing technologies including viral and non-viral delivery of the CRISPR/Cas9 genome editing system, and we summarize the strengths and limitations of each technology. We then discuss possible avenues for future research, including the development of organ-specific EC genome editing technologies. In short, EC-specific genome editing technologies can be used to modulate gene expression selectively in ECs and even within a specific vascular bed and/or distinctive EC subtype, and, in doing so, greatly improve the understanding of vascular biology and help develop precision genetic medicine targeting the disease-causing vascular bed(s) to effectively treat diseases caused by vascular endothelial dysfunction. Full article