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Myocardin related t...
Myocardin related transcription factor and galectin-3 drives lipid accumulation in human blood vessels
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- Arévalo-Martinez, Marycarmen (författare)
- Lund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups
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- Ede, Jacob (författare)
- Lund University,Lunds universitet,Neurologiska skador vid akut aortadissektion typ A,Forskargrupper vid Lunds universitet,Neurological injury in acute type A aortic dissection,Lund University Research Groups,Skåne University Hospital
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- van der Have, Oscar (författare)
- Lund University,Lunds universitet,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Vessel Wall Biology,Lund University Research Groups,Cardiovascular Research - Immunity and Atherosclerosis
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- Ritsvall, Olivia (författare)
- Lund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups
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- Zetterberg, Fredrik R (författare)
- Galecto Biotech AB, Sweden
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- Nilsson, Ulf J (författare)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Galecto Biotech AB, Sweden
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- Leffler, Hakon (författare)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Holmberg, Johan (författare)
- Lund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups
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- Albinsson, Sebastian (författare)
- Lund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: Vascular Pharmacology. - 1537-1891. ; 156
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Atherosclerosis
- Diabetes
- Dyslipidemia
- Mechanosensing
- MKL1
- Vascular smooth muscle
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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