Pub Date : 2024-06-01DOI: 10.1016/j.vph.2024.107383
Marycarmen Arévalo-Martinez , Jacob Ede , Oscar van der Have , Olivia Ritsvall , Fredrik R. Zetterberg , Ulf J. Nilsson , Hakon Leffler , Johan Holmberg , Sebastian Albinsson
Objective
Diabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis.
Approach and results
Human mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading.
Conclusion
Ex vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.
{"title":"Myocardin related transcription factor and galectin-3 drive lipid accumulation in human blood vessels","authors":"Marycarmen Arévalo-Martinez , Jacob Ede , Oscar van der Have , Olivia Ritsvall , Fredrik R. Zetterberg , Ulf J. Nilsson , Hakon Leffler , Johan Holmberg , Sebastian Albinsson","doi":"10.1016/j.vph.2024.107383","DOIUrl":"10.1016/j.vph.2024.107383","url":null,"abstract":"<div><h3>Objective</h3><p>Diabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels <em>ex vivo</em> can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/<em>LGALS3</em>. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis.</p></div><div><h3>Approach and results</h3><p>Human mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading.</p></div><div><h3>Conclusion</h3><p><em>Ex vivo</em> organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141234706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.vph.2024.107326
Mirko Hu , Flavia Bonalumi , Minh Long Hoan , Margherita Burattini , Alessia Caputo , Valentina Bollati , Barbara Montanini , Stefano Rossi , Nicola Delmonte , Michele Miragoli
{"title":"Assessing the impact of air pollution on human embryonic cardioids using innovative longitudinal monitoring and machine learning","authors":"Mirko Hu , Flavia Bonalumi , Minh Long Hoan , Margherita Burattini , Alessia Caputo , Valentina Bollati , Barbara Montanini , Stefano Rossi , Nicola Delmonte , Michele Miragoli","doi":"10.1016/j.vph.2024.107326","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107326","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.vph.2024.107349
Jessica Gambardella , Stanislovas S. Jankauskas , Urna Kansakar , Fahimeh Varzideh , Roberta Avvisato , Gaetano Santulli
{"title":"COVID-19 causes the opening of the mitochondrial permeability transition pore in human endothelial cells","authors":"Jessica Gambardella , Stanislovas S. Jankauskas , Urna Kansakar , Fahimeh Varzideh , Roberta Avvisato , Gaetano Santulli","doi":"10.1016/j.vph.2024.107349","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107349","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.vph.2024.107299
Silvia Berrettoni , Michelle Mendiola Pla , Franklin H. Lee , Giacomo Rozzi , Ryan T. Gross , Amy Evans , David C. Wendell , Paul Lezberg , Margherita Burattini , Francesco Paolo lo Muzio , Lorenzo Fassina , Carmelo A. Milano , Marie-Louise Bang , Dawn E. Bowles , Michele Miragoli
{"title":"Video analysis of ex-vivo beating hearts during preservation on the TransMedics® organ care system","authors":"Silvia Berrettoni , Michelle Mendiola Pla , Franklin H. Lee , Giacomo Rozzi , Ryan T. Gross , Amy Evans , David C. Wendell , Paul Lezberg , Margherita Burattini , Francesco Paolo lo Muzio , Lorenzo Fassina , Carmelo A. Milano , Marie-Louise Bang , Dawn E. Bowles , Michele Miragoli","doi":"10.1016/j.vph.2024.107299","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107299","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.vph.2024.107337
David Molla , Anthony Frosio , Giorgia Bertoli , Chiara Piantoni , Martina Arici , Chiara Bartolucci , Procolo Marchese , Claudia Bazzini , Andrea Barbuti , Marcella Rocchetti , Stefano Severi , Annalisa Bucchi , Mirko Baruscotti
{"title":"In-vitro studies of the NaV1.5 S805L Brugada mutation: The resting cell voltage is a critical element in determining the pathological or physiological phenotype of the current","authors":"David Molla , Anthony Frosio , Giorgia Bertoli , Chiara Piantoni , Martina Arici , Chiara Bartolucci , Procolo Marchese , Claudia Bazzini , Andrea Barbuti , Marcella Rocchetti , Stefano Severi , Annalisa Bucchi , Mirko Baruscotti","doi":"10.1016/j.vph.2024.107337","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107337","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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