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Kuanxiong aerosol protects against coronary microvascular dysfunction through improving angiogenesis via HIF-1α-ITGAX axis
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DOI:10.3389/fphar.2026.1881934.png)
Abstract
En 中文
BackgroundCoronary microvascular dysfunction (CMVD) frequently complicates diabetes mellitus and serves as a major driver of cardiovascular morbidity; underscoring the urgent need for innovative therapeutic strategies. Kuanxiong aerosol (KX); a patented botanical formulation of four volatile oils widely used for angina; possesses established vasoprotective and hemodynamic benefits. However; its efficacy and mechanisms in CMVD remain uncharacterized.MethodsTo evaluate the therapeutic potential of KX; both preventive and therapeutic treatment regimens were administered to a db/db mouse model of diabetic CMVD. In vivo therapeutic effects were comprehensively assessed using echocardiography and histopathological analyses. Microvascular perfusion and endothelial barrier function were quantitatively evaluated via Lectin-FITC perfusion and permeability assays.These findings were further corroborated by bulk RNA sequencing; immunofluorescence; and cellular functional assays; while bioinformatics and biochemical analyses systematically revealed the molecular targets and pathways.ResultsKX restored coronary microvascular structure and function; promoting neovascularization and conferring both preventive and therapeutic benefits against CMVD in db/db mice. Mechanistically; RNA sequencing and biochemical analyses revealed that KX stabilizes HIF-1α against PHD2-mediated proteasomal degradation. This stabilization enhances HIF-1α transcriptional activity to upregulate ITGAX; which subsequently triggers the VEGF-FAK signaling pathway to drive endothelial proliferation; angiogenesis and tight junction formation. Consequently; the improved microvascular function and stabilized nascent vascular network restore myocardial blood supply; thereby rescuing CMVD.ConclusionKX exerts its therapeutic effects through modulation of the HIF-1α–ITGAX axis; thereby promoting angiogenesis and restoring microvascular integrity and perfusion. These findings establish KX as a promising therapeutic candidate for CMVD and diabetic cardiomyopathy.
Keywords:
diabetes mellitus
angiogenesis
coronary microvascular dysfunction
Kuanxiong aerosol
HIF-1α-ITGAX axis
VEGF-FAK pathway
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