ArticleBMC medicine2023
Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 29 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Gestational diabetes as an inter-generational cardiometabolic risk factor: spotlight on emerging exerkines.Cardiovascular diabetology · 2026Review
- Causal role of adipose tissue-derived adipokines in the pathogenesis of heart failure with preserved ejection fraction: experimental demonstration as the basis for clinical targeting.European heart journal · 2026Article
- Advances in the application of nanoparticles for the diagnosis and treatment of diabetic cardiomyopathy.Frontiers in cell and developmental biology · 2026Review
- Astragaloside IV prevents calpain-1-mediated cardiac hypertrophy and fibrosis induced by diabetes.Frontiers in cardiovascular medicine · 2026Article
- Diabetic Atrial Cardiomyopathy: Pathogenesis, Diagnosis, Management, AI-Driven Diagnosis, and Risk Prediction.Journal of diabetes research · 2026Review
- Methylmalonate accumulation contributes to myocardial vulnerability post-reperfusion: a novel therapeutic target and prognostic biomarker.BMC medicine · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- EGLN1 inhibition reverses angiogenesis impairment in hyperglycemia by activating autophagy.Scientific reports · 2025Article
- The heart of diabetes: unraveling metabolic drivers of cardiomyopathy.Cardiovascular diabetology. Endocrinology reports · 2025Review
- Deep phenotyping of a modified diabetic cardiomyopathy mouse model which reflects clinical disease progression.Diabetology & metabolic syndrome · 2025Article
- Review
- The impact of diabetes mellitus on blood-tissue barrier regulation and vascular complications: Is the lung different from other organs?Tissue barriers · 2025Review
- Exploring the key target molecules of angiogenesis in diabetic cardiomyopathy based on bioinformatics analysis.Frontiers in endocrinology · 2025Article
- Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis.Cardiovascular diabetology · 2024Article
- Adiposity and Mineral Balance in Chronic Kidney Disease.Current osteoporosis reports · 2024Review
- The role of nonmyocardial cells in the development of diabetic cardiomyopathy and the protective effects of FGF21: a current understanding.Cell communication and signaling : CCS · 2024Review
- Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.Acta pharmacologica Sinica · 2024Article
- The mechanisms and therapeutic potential of clopidogrel in mitigating diabetic cardiomyopathy in db/db mice.iScience · 2024Article
- Role of complement factor D in cardiovascular and metabolic diseases.Frontiers in immunology · 2024Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicrovascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive.
methodsExperimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (Adipsin
resultsThe results showed that Adipsin overexpression significantly reduced cardiac microvascular permeability, preserved coronary microvascular integrity, and increased coronary microvascular density. Adipsin overexpression also attenuated cardiac dysfunction in diabetic mice. E/A ratio, an indicator of cardiac diastolic function, was improved by Adipsin. Adipsin overexpression retarded left ventricular adverse remodeling, enhanced LVEF, and improved cardiac systolic function. Adipsin-enriched exosomes were taken up by CMECs, inhibited CMECs apoptosis, and increased CMECs proliferation under HG + PA treatment. Adipsin-enriched exosomes also accelerated wound healing, rescued cell migration defects, and promoted tube formation in response to HG + PA challenge. Furthermore, Adipsin-enriched exosomes maintained adherens junctions at endothelial cell borders and reversed endothelial hyperpermeability disrupted by HG + PA insult. Mechanistically, Adipsin blocked HG + PA-induced Src phosphorylation (Tyr416), VE-cadherin phosphorylation (Tyr685 and Tyr731), and VE-cadherin internalization, thus maintaining CMECs adherens junctions integrity. LC-MS/MS analysis and co-immunoprecipitation analysis (Co-IP) unveiled Csk as a direct downstream regulator of Adipsin. Csk knockdown increased Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685 and Tyr731), while abolishing Adipsin-induced inhibition of VE-cadherin internalization. Furthermore, Csk knockdown counteracted Adipsin-induced protective effects on endothelial hyperpermeability in vitro and endothelial barrier integrity of coronary microvessels in vivo.
conclusionsTogether, these findings favor the vital role of Adipsin in the regulation of CMECs adherens junctions integrity, revealing its promises as a treatment target against diabetic coronary microvascular dysfunction. Graphical abstract depicting the mechanisms of action behind Adipsin-induced regulation of diabetic coronary microvascular dysfunction.
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