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Effects of metformin and empagliflozin on runt- related transcription factor-2 (RUNX2) mRNA expression in vascular calcification of metabolic syndrome rats

Heart Science Journal · Vol. 7 No. 4 (2026) · hlm. 22–27

DOI
10.21776/ub.hsj.2026.007.04.5
ISSN
2721-9984, 2721-9976
Terbit
2026-10-13
Penerbit
Universitas Brawijaya
Bahasa
en
Lisensi
creativecommons.org/licenses/by/4.0

Abstrak

Background: Vascular calcification (VC) is a severe vascular complication of metabolic syndrome (MetS), strongly correlated with increased cardiovascular morbidity and mortality. One of the most important regulator of osteoblastic differentiation, runt-related transcription factor-2 (RUNX2) has a crucial role in VC by promoting the transformation of vascular smooth muscle cells (VSMCs) toward an osteoblast-like phenotype.Objective: This study explored the effect of MetS on VC by raising RUNX2 mRNA expression and how metformin and empagliflozin affect RUNX2 mRNA expression in MetS-induced rats.Methods: Twenty Sprague-Dawley male rats were randomly separated into four groups: negative control (NC), MetS, MetS treated with metformin 500 mg/kgBW/day, and MetS treated with empagliflozin 30 mg/kgBW/day. MetS was induced by a high-fat high-sucrose diet and low-dose streptozotocin injection. RUNX2 mRNA expression was measured using RT-PCR and aortic tissue was stained using hematoxylin-eosin.Result: MetS induction resulted in visible microcalcification within the aortic wall and significantly increased RUNX2 mRNA expression compared with the NC group (mean ± SD: 38 ± 15, p = 0.01), indicating enhanced VC. Metformin markedly reduced RUNX2 mRNA expression (mean ± SD: 73 ± 7, p = 0.03), whereas empagliflozin showed a non-significant decrease (mean ± SD: 76 ± 23, p = 0.87). Conclusion: MetS induction can stimulate VC accompanied by increased RUNX2 mRNA expression in rats aortic tissue. Metformin and empagliflozin mitigate these changes, with metformin showing a more pronounced effect. This strengthens the importance of controlling MetS to reduce the risk of VC.

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Anna Fuji RahimahAfiliasi tidak diketahui23
Ardian RizalAfiliasi tidak diketahui21
Indra PrasetyaAfiliasi tidak diketahui20
Cholid Tri TjahjonoAfiliasi tidak diketahui20
Budi SatrijoAfiliasi tidak diketahui18
Setyasih AnjarwaniAfiliasi tidak diketahui18
Heny MartiniAfiliasi tidak diketahui13
Novi KurnianingsihAfiliasi tidak diketahui12
Djanggan SargowoAfiliasi tidak diketahui9
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Sasmojo WiditoAfiliasi tidak diketahui9
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Adhika Prastya WikanandaAfiliasi tidak diketahui4
Tri AstiawatiAfiliasi tidak diketahui4
Dadang HendrawanAfiliasi tidak diketahui3
Muhammad Rizki FadlanAfiliasi tidak diketahui3
Hayla Iqda MillisaniAfiliasi tidak diketahui3
Nikhen NoverikeAfiliasi tidak diketahui3
Veny KurniawatiAfiliasi tidak diketahui2
Putri Annisa KamilaUniversity of Brawijaya2
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Olivia HandayaniAfiliasi tidak diketahui2
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Sumber metadata: OAI-PMH (metadata jurnal) https://heartscience.ub.ac.id/index.php/heartscience/oai, pertama di-harvest 8 Nov 2026, terakhir terlihat 8 Nov 2026.
Metadata asli (oai_dc) 
<oai_dc:dc xmlns="http://www.openarchives.org/OAI/2.0/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/  http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
	<dc:title xml:lang="en">Effects of metformin and empagliflozin on runt- related transcription factor-2 (RUNX2) mRNA expression in vascular calcification of metabolic syndrome rats</dc:title>
	<dc:creator xml:lang="en">Christine, Anastasia</dc:creator>
	<dc:creator xml:lang="en">Rohman, Mohammad Saifur</dc:creator>
	<dc:creator xml:lang="en">Yogibuana, Valerinna</dc:creator>
	<dc:subject xml:lang="en">Vascular calcification</dc:subject>
	<dc:subject xml:lang="en">metabolic syndrome</dc:subject>
	<dc:subject xml:lang="en">RUNX2</dc:subject>
	<dc:subject xml:lang="en">metformin</dc:subject>
	<dc:subject xml:lang="en">empaglifozin</dc:subject>
	<dc:description xml:lang="en">Background: Vascular calcification (VC) is a severe vascular complication of metabolic syndrome (MetS), strongly correlated with increased cardiovascular morbidity and mortality. One of the most important regulator of osteoblastic differentiation, runt-related transcription factor-2 (RUNX2) has a crucial role in VC by promoting the transformation of vascular smooth muscle cells (VSMCs) toward an osteoblast-like phenotype.Objective: This study explored the effect of MetS on VC by raising RUNX2 mRNA expression and how metformin and empagliflozin affect RUNX2 mRNA expression in MetS-induced rats.Methods:  Twenty Sprague-Dawley male rats were randomly separated into four groups: negative control (NC), MetS, MetS treated with metformin 500 mg/kgBW/day, and MetS treated with empagliflozin 30 mg/kgBW/day. MetS was induced by a high-fat high-sucrose diet and low-dose streptozotocin injection. RUNX2 mRNA expression was measured using RT-PCR and aortic tissue was stained using hematoxylin-eosin.Result: MetS induction resulted in visible microcalcification within the aortic wall and significantly increased RUNX2 mRNA expression compared with the NC group (mean ± SD: 38 ± 15, p = 0.01), indicating enhanced VC. Metformin markedly reduced RUNX2 mRNA expression (mean ± SD: 73 ± 7, p = 0.03), whereas empagliflozin showed a non-significant decrease (mean ± SD: 76 ± 23, p = 0.87). Conclusion: MetS induction can stimulate VC accompanied by increased RUNX2 mRNA expression in rats aortic tissue. Metformin and empagliflozin mitigate these changes, with metformin showing a more pronounced effect. This strengthens the importance of controlling MetS to reduce the risk of VC.</dc:description>
	<dc:publisher xml:lang="en">Universitas Brawijaya</dc:publisher>
	<dc:date>2026-10-13</dc:date>
	<dc:type>info:eu-repo/semantics/article</dc:type>
	<dc:type>info:eu-repo/semantics/publishedVersion</dc:type>
	<dc:format>application/pdf</dc:format>
	<dc:identifier>https://heartscience.ub.ac.id/index.php/heartscience/article/view/20587</dc:identifier>
	<dc:identifier>10.21776/ub.hsj.2026.007.04.5</dc:identifier>
	<dc:source xml:lang="en">Heart Science Journal; Vol. 7 No. 4 (2026): Navigating High-Risk Cardiovascular Subsets: Premature Disease, Plaque Complexity, and Precision Interventions; 22-27</dc:source>
	<dc:source>2721-9984</dc:source>
	<dc:source>2721-9976</dc:source>
	<dc:source>10.21776/ub.hsj.2026.007.04</dc:source>
	<dc:language>en</dc:language>
	<dc:relation>https://heartscience.ub.ac.id/index.php/heartscience/article/view/20587/616</dc:relation>
	<dc:rights xml:lang="en">Copyright (c) 2026 Anastasia Christine</dc:rights>
	<dc:rights xml:lang="en">http://creativecommons.org/licenses/by/4.0</dc:rights>
</oai_dc:dc>