Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and its progression is closely linked to mitochondrial dysfunction in cardiomyocytes. Given the high energy demands of the heart, precise regulation of mitochondrial homeostasis, including oxidative phosphorylation, reactive oxygen species balance, calcium handling, and mitophagy, is essential for maintaining cardiac function. Emerging evidence has identified mitochondrial-associated long non-coding RNAs (mito-lncRNAs) as important regulators of these processes. Mito-lncRNAs comprise both nuclear-encoded transcripts that translocate to mitochondria and mitochondrial genome-encoded lncRNAs that function within the organelle. These molecules modulate mitochondrial gene expression, respiratory chain stability, metabolic flux, and stress responses, thereby influencing the pathogenesis of acute myocardial infarction, heart failure, diabetic cardiomyopathy, pulmonary hypertension, and cardiac remodeling. In this review, we categorize mito-lncRNAs based on their genomic origin and mitochondrial localization and summarize their mechanistic roles in cardiovascular physiology and disease. Moreover, the review highlights context-dependent effects of key transcripts such as LIPCAR, MALAT1, RMRP, H19, and lncND5. We further discuss the emerging value of mito-lncRNAs as circulating biomarkers and examine the major challenges that currently limit therapeutic translation, including cardiac- and mitochondrial-specific delivery, mechanistic ambiguity, species conservation, and technical limitations in detection. A deeper understanding of mito-lncRNA biology may provide new insights into mitochondrial regulation in the heart and inform the development of novel diagnostic and therapeutic strategies for CVDs.

Pulmonary hypertension (PH) is a heterogeneous condition with variable prognosis across World Health Organization (WHO) subtypes. The fasting blood glucose to high-density lipoprotein cholesterol (FBG/HDL-C) ratio has been suggested as a metabolic predictor of adverse outcomes in critically ill patients, but its prognostic value in PH remains unclear. This retrospective cohort included 281 ICU patients with pulmonary hypertension (PH) from MIMIC-IV (2008-2022). Patients were divided into tertiles based on ln(1 + FBG/HDL-C). The primary endpoint was 90-day all-cause mortality, which was assessed using Cox proportional hazards regression, with exploratory subgroup analyses by WHO PH groups. In fully adjusted models, patients in the highest tertile of ln(1 + FBG/HDL-C) had higher 90-day mortality than those in the lowest tertile (HR = 3.30, 95% CI: 1.82, 5.97; p < 0.001). Elevated risk was observed across WHO PH Groups 1, 2, and 5, with the most statistically robust and clinically interpretable association in Group 2 (HR = 2.66, 95% CI: 1.40, 5.05; p = 0.003). Elevated FBG/HDL-C ratio was independently associated with 90-day mortality, with the association in Group 2 being the most statistically stable and clinically interpretable.

With improving survival, periviable neonates (≤25 weeks' gestation) represent a dynamic, but under-studied population in neonatal care, with persistently high cardiopulmonary and vascular vulnerability. Immature cardiovascular structure and function as a consequence of immature myocardial architecture, altered calcium handling, relative adrenal insufficiency, and persistent fetal shunts contribute to complex and dynamic cardiovascular physiology in this population. This may be present clinically in the form of hypotension and low end-organ perfusion. Traditional paradigms of blood pressure-based definitions of hypotension are poorly validated in this population and do not accurately reflect systemic blood flow or end-organ perfusion. Emerging evidence supports a phenotype-based multi-parametric approach to cardiovascular assessment, to distinguish ongoing physiological changes such as ductal physiology, pulmonary hypertension, low systemic vascular resistance and primary myocardial dysfunction phenotypes. However, significant knowledge gaps remain, including lack of normative hemodynamic values, and limited evidence guiding pharmacologic therapies. This narrative review focuses on the cardiovascular challenges in the management of periviable neonates as they transition to extrauterine life, delineating cardiac phenotypes, describing modalities of cardiovascular assessment and identifying existing knowledge gaps. We propose a physiology-based approach to cardiovascular management strategies based on existing, albeit limited, evidence. IMPACT: Periviable neonates present unique hemodynamic challenges due to structural and functional cardiovascular system immaturity, which can be categorized into different hemodynamic phenotypes dictated by baseline cardiac function, lung compliance and directionality of intracardiac shunts, especially the patent ductus arteriosus. In the absence of established normative reference values for common modalities of cardiac assessment, optimal care should consist of early identification of cardiac phenotypes, continuous surveillance, physiology-based management strategies, and frequent reassessment to guide individualized treatment.

Brahma-related gene 1 (Brg1) is a major factor in regulation of chromatin remodeling and is involved in different cellular processes, including cell proliferation, apoptosis, and differentiation. However, the role of Brg1 in pulmonary artery hypertension (PAH) has not been elucidated. This study aims to assess the role of Brg1 in PAH using hypoxia-induced PAH rat model, Monocrotaline(MCT)-induced PAH rat model, and hypoxia-induced arterial smooth muscle cell model. We found that Brg1 expression was highly expressed in hypoxia-induced PAH rat model and MCT-induced PAH rat model. Moreover, knockdown of Brg1 by injection of adenoviral Brg1 shRNA inhibited Nrf2 expression and its downstream molecular HO-1, attenuated apoptosis resistance, and ameliorated PAH progression in PAH rats. Meanwhile, knockdown of Brg1 suppressed cell proliferation through downregulating the expression of mTOR/P70S6K signaling pathway in vitro and in vivo. In addition, the Nrf2 inhibitor Brusatol treatment significantly inhibited cell proliferation, whereas abrogated by loss of Brg1. In summary, these results demonstrated that loss of Brg1 inhibited PAH progression by downregulating Nrf2 to attenuate cell proliferation and enhance apoptosis, which may provide a new therapeutic target to improve cardiopulmonary function in PAH patients.

Menopause is accompanied by loss of ovarian estrogen and progesterone production and by age-related changes in circulating androgens, with implications for respiratory physiology and chronic pulmonary disease. Sex steroids influence lung development, immune responses, airway tone, vascular remodeling and pathways involved in lung carcinogenesis. Epidemiological evidence linking menopausal hormone therapy (MHT) to asthma is heterogeneous; some cohorts show increased incident asthma or exacerbations, particularly with estrogen therapy and in specific subgroups, whereas others suggest preserved lung function or reduced late-onset asthma. Data on chronic obstructive pulmonary disease remain limited and inconsistent. In pulmonary hypertension, evidence is conflicting, and clinical decisions must weigh thrombotic risk, strongly influenced by the route of estrogen administration. Studies on obstructive sleep apnea and sleep-disordered breathing suggest possible modest benefits of MHT in selected populations but are methodologically heterogeneous. For lung cancer, large cohorts, meta-analyses and randomized trials essentially show no clear increase in incidence with MHT and suggest potential survival advantages in some subgroups. Overall, MHT use in women with or at risk for pulmonary disease should be individualized, integrating symptom burden, cardiometabolic and respiratory risk, disease phenotype and formulation/route.

Pulmonary embolism (PE) is one of the leading causes of cardiovascular mortality in the United States. Even in those patients who get treatment in the acute phase, they are at risk of developing pulmonary hypertension, recurrent PE, which can lead to functional impairment and decreased survival. Interventional therapies for PE are reserved for unstable patients with high-risk PE or stable patients at high risk for decompensation. Several large-bore devices are currently approved for the treatment of PE and can provide expeditious thrombus removal without the need for lytic agents. Here, we review some of the large-bore catheter devices available for the treatment of acute PE.

Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality worldwide. Effective management hinges on accurate risk stratification - classifying patients as high, intermediate, or low risk - to guide reperfusion strategies. This review evaluates the contemporary role of systemic thrombolysis, with a focus on the balance between rapid hemodynamic restoration and the risk of catastrophic hemorrhage. For high-risk PE characterized by hemodynamic instability, systemic thrombolysis remains the gold standard, offering a significant survival benefit that outweighs bleeding risks. Conversely, in intermediate-risk PE, it has been demonstrated that while full-dose thrombolysis prevents hemodynamic decompensation, it is associated with a significant increase in major bleeding and intracranial hemorrhage. Consequently, current guidelines generally support a "rescue thrombolysis" strategy rather than routine, up-front administration in this population. Encouragingly, recent small studies appear to demonstrate reduced-dose protocols that maintain efficacy while minimizing risk of major bleeding. While the acute effects of thrombolysis on hemodynamics are clear, there is conflicting evidence regarding the impact of thrombolysis on long-term sequelae such as chronic thromboembolic pulmonary hypertension (CTEPH). Ultimately, clinical decision-making must prioritize immediate hemodynamic risk while carefully evaluating contraindications to minimize adverse outcomes.

Pulmonary arterial hypertension (PAH) is characterized by excessive remodeling of the proximal and distal arterioles, driven by endothelial cell apoptosis and uncontrolled mural cell proliferation. Increasing evidence suggests an important role of inflammation in PAH, but 1 crucial part of the immune system, the pulmonary lymphatics, has been largely overlooked. Patients with idiopathic PAH often develop abnormal tertiary lymphoid structures adjacent to remodeled arteries, yet the role of lymphatic vessels in PAH pathogenesis and vascular remodeling remains unclear. Using a mouse model to specifically label lymphatic endothelial cells (Prox1-CreERT2::Rosa26-LSL-tdT), we found that pulmonary lymphatic vessels proliferated and dilated in response to hypoxia. We further showed that Vegfr3 inhibition using MAZ51 reduced hypoxia induced lymphangiogenesis and was associated with severe pulmonary hypertension. Additionally, lymphatic endothelial cell-specific deletion of Vegfr3 (Prox1-CreERT2::Vegfr3[fl/fl]) prevents adaptive lymphangiogenesis and exacerbates pulmonary hypertension, resulting in right ventricular hypertrophy. Comparative single-cell RNA sequencing analysis of human idiopathic PAH and hypoxia-induced pulmonary hypertension mouse lungs revealed upregulation of CD74/Cd74 in lymphatic endothelial cell clusters, and in humans this was associated with enhanced expression of FLT4/VEGFR3 and downstream mediators in the MEK/ERK signaling pathway. Consistently, increased CD74 expression was observed in lymphatic vessels in human idiopathic PAH lung sections, and CD74 overexpression in human lymphatic cells was associated with impaired barrier permeability and coexpression of VEGFR3. Together, these findings provide novel insights into the role of lymphatic Cd74/CD74 activation in pulmonary hypertension development and suggest that therapies aimed at augmenting lymphatic function may improve outcomes in patients with PAH.

Pulmonary hypertension (PH) is a progressive and multifactorial disease marked by elevated pulmonary arterial pressure and right ventricular (RV) dysfunction. Among its subtypes, pulmonary arterial hypertension (PAH) is characterised by profound vascular remodelling, inflammation and fibrosis. Despite therapeutic advances targeting the endothelin, nitric oxide, prostacyclin, and, more recently, the activin signalling pathway via sotatercept, outcomes in PAH remain suboptimal, particularly in patients with cardiovascular comorbidities. This has prompted growing interest in novel metabolic-based interventions, such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs). GLP-1RAs, initially developed for type 2 diabetes and obesity, exhibit pleiotropic properties including vasodilation, anti-inflammatory, antifibrotic and endothelial-protective effects. In experimental models of PAH GLP-1RAs administration attenuates the severity of PH. Additional studies highlight their ability to protect against lung fibrosis and preserve endothelial function. Indirect enhancement of GLP-1 signalling through dipeptidyl peptidase-4 (DPP-4) inhibition similarly improves pulmonary haemodynamics and mitigates fibrosis and inflammation, underscoring the relevance of this pathway. Although no clinical trials have specifically evaluated GLP-1RAs in PH, observational studies in patients with heart failure with preserved ejection fraction suggest potential cardiopulmonary benefits. GLP-1RAs emerge as promising candidates bridging metabolic, vascular and cardiac domains in PH, warranting rigorous clinical validation. These findings support further translational research and randomised clinical trials to evaluate GLP-1RAs as a disease-modifying therapy in PAH.

Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disorder driven by pulmonary vascular remodeling, with high morbidity and mortality. Current therapies only alleviate symptoms and cannot reverse disease progression. Our previous study has demonstrated that microRNA-661 (miR-661) inhibits Human pulmonary artery smooth muscle cell (HPASMC) and Human pulmonary artery endothelial cell (HPAEC) proliferation, but its underlying molecular mechanism in PAH remains unclear. This study aimed to identify the target gene of miR-661 and elucidate its regulatory role in PAH pathogenesis, seeking novel therapeutic targets for this incurable disease.