semaxanib (SU5416) / Pfizer - LARVOL DELTA

PPARα Activation Attenuates Right Ventricular Hypertrophy by Regulating Myocardial Glucose and Lipid Metabolism in High-Altitude Pulmonary Hypertension In Vivo and In Vitro. (PubMed, High Alt Med Biol) - "In this study, our findings demonstrate that PPARα exerts a protective effect against RVH, at least in part, by promoting fatty acid oxidation through upregulation of its downstream target proteins CPT-1 and acyl-CoA oxidase 1."

Journal • Preclinical • Cardiovascular • Hypertension • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACOX1 • PPARA

Heterogeneous nuclear ribonucleoprotein A1 as a candidate associated with pulmonary vascular remodeling in pulmonary arterial hypertension. (PubMed, J Mol Cell Cardiol Plus) - "Proteomic remodeling was assessed before and after the formation of PLs in a SU5416 combined with hypoxia (SuHx) rat model of severe PAH using laser-capture microdissection coupled with mass spectrometry...Several DEPs associated with PL formation but with unclear relevance to pulmonary artery remodeling in PAH were discovered. Among these, hnRNPA1, which was not detected in transcriptome analysis and whole lung analysis, may be important in PL formation."

Heterogeneity • Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • PKM

Enhancing clearance of senescent endothelial cells by activation of lung-resident iNKT cells as a novel therapeutic strategy for pulmonary arterial hypertension (ERS 2026) - " PAH was induced using a single injection of the VEGFR inhibitor SU5416 (SU) and 3 weeks of hypoxia (10% O₂)... Enhancing lung senescent cell clearance by tissue-resident iNKT cells improves PAH, supporting a novel immunotherapeutic strategy for pulmonary vascular disease."

IO biomarker • Cardiovascular • Immunology • Pulmonary Arterial Hypertension • Respiratory Diseases

PUS7-Mediated Pseudouridylation of TGFBI Drives Vascular Remodeling in Pulmonary Hypertension. (PubMed, Circulation) - "PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells, the lung tissues of patients with PH, and SU5416-hypoxia rodent model...Furthermore, hypoxia-inducible factor 2α bound directly to the PUS7 promoter, establishing a hypoxia-inducible factor 2α/PUS7/TGFBI/phosphatidylinositol 3-kinase-protein kinase B positive feedback loop that drives PH pathogenesis. PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH through the hypoxia-inducible factor 2α/PUS7/TGFBI/phosphatidylinositol 3-kinase-protein kinase B axis, positioning PUS7 as a promising therapeutic target for this devastating disease."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • TGFBI

Anti‑ZIP12 mAb APL‑9796 Attenuates Fibrosis and Inflammation in Experimental Pulmonary Hypertension Rodent Model (ERS 2026) - "APL‑9796 was evaluated in vivo using the resiquimod–SU5416 (R‑SU) rat model, which recapitulates key features of Group 3 PH, including elevated pulmonary haemodynamics, perivascular inflammation and pulmonary fibrosis...Circulating pro‑inflammatory cytokines and chemokines, including CXCL1, CCL5, TNF‑α, CXCL10 and IL‑17, were also reduced. ConclusionsTargeting zinc homeostasis with APL‑9796 demonstrates potential as a disease‑modifying therapeutic strategy for Group 3 PH."

Preclinical • Cardiovascular • Fibrosis • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CXCL1 • CXCL10 • TIMP1 • TNFA • VIM

Identifying GSTM1, SDC1, and VTN as key biomarkers and therapeutic targets for NETs in acute pancreatitis based on bioinformatics analysis and experiments. (PubMed, Int Immunopharmacol) - "Furthermore, semaxanib may have potential associations with pathways related to GSTM1, SDC1 and VTN, thereby participating to some extent in the intervention of acute pancreatitis. These findings provide a foundation for precision medicine approaches in AP management."

Biomarker • Journal • Inflammation • Pancreatitis • GSTM1 • SDC1 • VTN

Splenic Focused Ultrasound Improves Experimental Pulmonary Hypertension and Reprograms Immune Responses in Female and Male Rats. (PubMed, Pulm Circ) - "In male and female animals, sFUS reduces pulmonary CD8+ T cells and CD68+ macrophages, and reduces splenic monocytes. Splenic single-cell transcriptomic analysis in the SU5416/hypoxia model revealed sex-specific immune responses, including persistent interferon signaling in males."

Journal • Preclinical • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CD68 • CD8

Impact of Hypoxia Duration and SU5416 Dose on SU5416-Hypoxia Model of Severe Pulmonary Arterial Hypertension (AHA 2026) - "Abstract is embargoed at this time."

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

Carboxymethyl Chitosan Promotes Osteogenesis Via p38/VEGFR2 and Shows Translational Potential in Sinus Floor Elevation. (PubMed, Int Dent J) - "CMCS promotes osteogenesis and mineralisation, at least partly via p38 MAPK and VEGF-VEGFR2 signalling. Retrospective clinical findings also indicate its potential utility in transcrestal sinus floor elevation."

Journal • KDR • RUNX2

The association of cardiovascular health with new-onset pulmonary hypertension and the mediating role of proteomic signatures. (PubMed, J Hypertens) - "High CVH level, defined by Life's Essential 8 (LE8), is significantly linked to a reduced risk of developing PH. This protective effect is primarily mediated by a proteomic signature, revealing the role of signaling pathways such as cytokine-cytokine receptor interaction in the prevention of PH."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • IL6

Polypharmacologic Disruption of the Proliferative-to-Mesenchymal Fate Branch Point Reverses EndMT and Pulmonary Hypertension. (PubMed, Res Sq) - "In the Su5416/hypoxia rat PH model, TK22 normalized right ventricular systolic pressure, Fulton index, and cardiac function. Together, these findings reframe pharmacologic EndMT control: inhibition at the proliferative-to-mesenchymal fate branch point, through coordinated suppression of cell-cycle and mesenchymal kinases, achieves high selectivity for erasing a pathological endothelial fate state. These findings propose TK22 as a mechanistically precise agent for EndMT-driven vascular disease and establish single-cell trajectory analysis as an essential readout of cellular target engagement and cell-state precision."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • AMPK • CDK2 • EGLN3 • MAP3K11 • NUAK1 • PACERR • PDGFRB • PFKFB3 • PTGS2 • SERPINE1 • SIK1 • TGFB1

Empagliflozin Ameliorates Experimental Pulmonary Vascular Remodeling, but May Not Benefit Patients With Pulmonary Arterial Hypertension. (PubMed, J Am Heart Assoc) - P2 | "Empagliflozin attenuates proliferation of PAH MVECs. Empagliflozin reduces pulmonary vascular remodeling in experimental PAH. While 12 weeks of empagliflozin treatment was feasible in patients with idiopathic or hereditary PAH, we observed signs of right ventricular deterioration."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Methylophiopogonanone A mitigates myocardial ischemia-reperfusion injury: involvement of VEGFR2-associated PI3K/Akt/GSK-3β signaling and suppression of mPTP opening. (PubMed, J Ethnopharmacol) - "MOA attenuates acute MIRI and preserves mitochondrial function. The findings support a model in which MOA-associated VEGFR2 target engagement and increased VEGFR2 protein stability are accompanied by enhanced PI3K/Akt signaling and inhibitory phosphorylation of GSK-3β. However, direct physical binding to VEGFR2 and classical VEGFR2 agonism were not established."

Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury • GSK3B • KDR

MiR-199a-3p deficiency induced by STAT3 activation drives smooth muscle cell phenotypic switching in pulmonary arterial hypertension. (PubMed, Noncoding RNA Res) - "Here, we report that miR-199a-3p is significantly downregulated in both hypoxia/SU5416-induced PAH rat models and PDGF-BB-stimulated human PASMCs...Collectively, these findings establish a PDGF-BB/STAT3/miR-199a-3p/YAP1 regulatory axis that drives pathological PASMC phenotypic switching. This axis represents a promising therapeutic target for mitigating pulmonary vascular remodeling in PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • MIR199A • MIR199A1 • STAT3 • YAP1

Hypoxia-Induced Epas1-Myl9/12 Axis Shapes the Pathology of Pulmonary Hypertension. (PubMed, Circ Res) - "To investigate the pathogenic role of Myl (myosin light chain) 9/12 in PH, we utilized the Sugen/hypoxia mouse model, generated by administration of the VEGF (vascular endothelial growth factor) receptor inhibitor SU5416 under hypoxic conditions (10% O2)...Moreover, serum levels of Myl9 but not MYL12A or MYL12B levels reflected the severity of PH in patients. These findings reveal that Myl9/12 play a pathogenic role in developing vascular lesions of PH and could be a new therapeutic target for PH."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombosis • EPAS1 • MYL9

Sitosterol-Beta mitigates pulmonary hypertension by targeting SPHK1 in mice. (PubMed, Arch Biochem Biophys) - "In our study, the PH was induced in mouse by chronic hypoxia insult (10% O2) and subcutaneous injection of vascular endothelial growth factor receptor inhibitor SU5416, and Sitosterol-Beta was delivered into mouse via orally taken...The effects of Sitosterol-Beta on PASMCs were abrogated by overexpression of SPHK1. In conclusion, this study demonstrated that Sitosterol-Beta improved PH in mouse by targeting SPHK1, which may provide novel insights for prevention and therapy of PH."

Journal • Preclinical • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • SPHK1

Integrative transcriptomic analysis identifies immune-associated candidate genes and altered immune cell infiltration in pulmonary arterial hypertension. (PubMed, PLoS One) - "This study identified BCLAF1, CDC5L, SMARCA5, and ASH1L as immune-associated hub genes in PAH and proposed a transcriptomic gene-immune prioritization framework. These candidates warrant further mechanistic investigation for their potential roles in PAH pathogenesis."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ASH1L • BCLAF1 • CTNNB1 • RBM39 • SMARCA5

Lipid nanoparticle-mediated metabolic reprogramming as a therapeutic strategy for pulmonary arterial hypertension (ASGCT 2026) - "Using this formulation, we evaluated siRNA-mediated Bdh1 knockdown (KD) via RT- qPCR and Western Blot, in control primary rat lung microvascular endothelial cells (RLMVECs) and RLMVECs isolated from the SU5416 Hypoxia (SuHx) model, which recapitulates many features of human PAH...Future work will examine the effect of Bdh1 downregulation on pulmonary vasoreactivity and right ventricular hypertrophy. Fig 1) A, B) Ex vivo imaging of rat organs following pDNA-Luc-LNP dose (0.75 mg kg-1, 24 h, i.v.) and total organ flux (n=6) C) % TdTomato expression of all live cells isolated from Ai9 mouse lungs following mRNA-Cre-LNP dose (0.4 mg kg-1 , 24 h, i.v., n=3) D) Total BAL cell count following mRNA-Cre-LNP administration (0.4 mg kg-1, 24 h, i.v. n=3) E) Bdh1 transcript levels of normoxic and SuHx MVECs after LNP-siRNA-Bdh1 versus NT (250 nM, 48 h, n=3) F) Intracellular BOHB levels following LNP-siRNA-Bdh1 versus NT (250 nM, 48 h, n=6)."

Cardiovascular • Metabolic Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases

Electroacupuncture Ameliorates Depressive-Like Behaviors by Enhancing Autophagy to Attenuate Hippocampal Neuroinflammation via the VEGF/AKT1/ERK Pathway in CUMS Rats. (PubMed, Neurochem Res) - "Rats were divided into control, CUMS, EA, EA + VEGFR2 inhibitor (SU5416) (EA+SU5416), EA + 3-methyladenine (3-MA), and FXL (fluoxetine) groups. Furthermore, the autophagy inhibitor 3-MA also blocked EA's benefits, indicating autophagy as the essential downstream executor. EA ameliorated depressive-like behaviors in CUMS rats, suggesting that the mechanism may involve the activation of the VEGF/AKT1/ERK pathway, leading to enhanced autophagy and attenuated hippocampal neuroinflammation."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Psychiatry • IL1B • TNFA

Targeted Delivery of GLUT1 Inhibitor via Macrophage Nanovesicles for Pulmonary Arterial Hypertension Therapy. (PubMed, J Extracell Vesicles) - "In mouse models of PAH induced by MCT and SU5416 combined with hypoxia, Mac@WZB117 effectively targeted pulmonary vascular lesions, leading to a significant reversal of arterial thickening and collagen deposition...Spatial transcriptomics analysis confirmed the spatial reorganization of hyperactive M1 macrophages from lesion regions. Overall, Mac@WZB117 delivers WZB117 precisely to M1 macrophages, suppressing their pro-inflammatory and metabolic functions to remodel the immune microenvironment and reverse vascular structural changes, suggesting a promising therapeutic approach for PAH and other immuno-metabolic diseases."

Journal • Cardiovascular • Hypertension • Inflammation • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • SLC2A1 • TGFB1

Amonafide Targeting NTSR1-PI3K/AKT/mTOR Signaling Attenuates Vascular Remodeling in Pulmonary Arterial Hypertension. (PubMed, J Am Heart Assoc) - "Our findings unveil the pivotal role of amonafide in PAH pathogenesis and suggest that targeting topoisomerase II α and NTSR1 may be a promising therapeutic approach for treating PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • mTOR

YWHAZ-mediated metabolic reprogramming via HIF1A/LDHA signaling promotes pulmonary arterial remodelling. (PubMed, Cell Death Discov) - "This study investigated YWHAZ's role in PAH using hypoxia-induced pulmonary arterial endothelial cells (PAECs) and a hypoxia/SU5416-induced PAH rat model...HIF-1α agonist treatment reversed YWHAZ silencing effects, confirming the YWHAZ/HIF-1α/LDHA axis. These findings highlight YWHAZ as a potential therapeutic target for metabolic intervention in PAH."

Journal • Cardiovascular • Hypertension • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • HIF1A • LDHA • YWHAZ

VEGFR-2 blocker induces pulmonary vascular disease in rats with CRISPR-edited human non-deficient G6PD polymorphism: role of 3D genomic modifications and DNA methylation. (PubMed, Br J Pharmacol) - "This suggests that our findings reflect a heretofore unknown connection between G6PD polymorphisms and the 3D genomic organization that controls VEGFR blocker-induced expression of DNA/histone demethylases. Potential effects include up-regulation of genes encoding proteins, which evoke cell migration and inflammation within the lungs and contribute to the pathogenesis of PVD."

Journal • Preclinical • Cardiovascular • Hypertension • Inflammation • Oncology • Pneumonia • Pulmonary Disease • IL1B • KDR

Defining the role of PINK1/Parkin dependent mitophagy in Right Ventricular Dysfunction and Cardiomyocyte Impairment in experimental Pulmonary Hypertension (PAS 2026) - "We found significantly decreased RV mitophagy following hypoxic exposure in mt-Keima reporter mice. We also found significantly reduced expression of PINK1 and Parkin in the RV of SU5416/hypoxia-exposed mice. PINK1-/- and Parkin-/- mice had markedly decreased tricuspid annular plane systolic excursion (TAPSE), increased RV fibrosis, and higher Fulton's index following SU5416/hypoxia exposure compared to WT mice."

Cardiovascular • Fibrosis • Heart Failure • Immunology • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ANXA5 • CD31 • PECAM1 • PINK1 • THY1

Global knockout of melanoma differentiation-associated protein 5 protects mice from chronic hypoxia/SU5416-induced pulmonary hypertension. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "Knockdown of MDA5 in macrophage-like cells reduced the type I interferon gene signature. Our data suggest a protective effect of whole-body MDA5 knockout in mice, which may be due to reduced immune dysregulation."

Journal • Preclinical • Cardiovascular • Hypertension • Melanoma • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Solid Tumor • IFIH1 • ITGAM