{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:12Z","timestamp":1786602432391,"version":"build-2736575974"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Coronary 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KX 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-1\u03b1 against PHD2-mediated proteasomal degradation. This stabilization enhances HIF-1\u03b1 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>KX exerts its therapeutic effects through modulation of the HIF-1\u03b1\u2013ITGAX axis, thereby promoting angiogenesis and restoring microvascular integrity and perfusion. These findings establish KX as a promising therapeutic candidate for CMVD and diabetic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1881934","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:32:40Z","timestamp":1786599160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Kuanxiong aerosol protects against coronary microvascular dysfunction through improving angiogenesis via HIF-1\u03b1-ITGAX axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuanqing","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University; State Key Laboratory of Transvascular Implantation Devices; Heart Regeneration and Repair Key Laboratory of Zhejiang Province","place":["Hangzhou, China"]},{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Qian","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibo","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"OuYang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Shi","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Research Institute of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University; State Key Laboratory of Transvascular Implantation Devices; Heart Regeneration and Repair Key Laboratory of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University; State Key Laboratory of Transvascular Implantation Devices; Heart Regeneration and Repair Key Laboratory of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12933-019-0820-6","article-title":"SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic Ob\/Ob","volume":"18","author":"Adingupu","year":"2019","journal-title":"Cardiovasc Diabetol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in heart failure with a preserved ejection fraction","volume":"385","author":"Anker","year":"2021","journal-title":"N. 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